Hitachi and ThinkCyte announce collaboration to develop an AI-driven cell analysis and sorting system – BioSpace

TOKYO, July 1, 2020 /PRNewswire/ --Hitachi, Ltd.(TSE: 6501, "Hitachi") and ThinkCyte, Inc. ("ThinkCyte") today announced that they have entered into a collaboration focused on developing an artificial intelligence (AI)-driven cell analysis and sorting system. Hitachi provides a broad range of solutions such as automated cell culture technologies to pharmaceutical companies in the value chain*1 of the regenerative medicine and cell therapy industry. Through the addition of this cell analysis and sorting system to the value chain, Hitachi continues contributing to cost reductions in the manufacturing of regenerative medicine and cell therapy products.Further, Hitachi and ThinkCyte are promoting collaboration with pharmaceutical companies and research institutes working in the field of regenerative medicine and cell therapy to expedite the development of the system toward commercialization.

The practical applications of regenerative medicine and cell therapy using cells for treatment have been expanding rapidly with the first regulatory approval of CAR-T*2 therapy for leukemia in 2017 in the United States and 2019 in Japan. The global market for regenerative medicine and cell therapy is expected to grow from US$ 5.9 billion (JPY 630 billion) in 2020 to US$ 35.4 billion (JPY 3.8 trillion) in 2025*3. In order to scale up treatment using regenerative medicine and cell therapy products, it is critical to ensure consistent selection and stable supply of high quality cells in large quantities and at a low costs.

Hitachi has been providing large-scale automated induced pluripotent stem (iPS) cell culture equipment, cell processing facilities (CPFs), manufacturing execution systems(MES), and biosafety cabinets among other products to pharmaceutical companies and research institutes, and has developed a value chain to meet a variety of customer needs in the regenerative medicine and cell therapy industry. Hitachi has also been carrying out collaborative research projects with universities, research institutes, and other companies to develop core technologies for pharmaceutical manufacturing instruments and in vitro diagnostic medical devices, prototyping for mass production, and working on manufacturing cost reduction and the development of stable and reliable instruments.

ThinkCyte has been performing research and development focused on high-throughput single cell analysis and sorting technology to precisely analyze and isolate target cells. While such single cell analysis and sorting technologies are vital to life science and medical research, it has been thought impossible to achieve high-throughput cell sorting based on high-content image information of every single cell. ThinkCyte has developed the world's first Ghost Cytometrytechnology to achieve high-throughput and high-content single cell sorting*4and has been conducting collaborative research projects with multiple pharmaceutical companies and research institutes to utilize this technology in life science and medical fields.

Hitachi and ThinkCyte have initiated a joint development of the AI-driven cell analysis and sorting system based on their respective technologies, expertise, and know-how. By combining ThinkCyte's high-throughput and high-content label-free single cell sorting technology and Hitachi's know-how and capability to producing stably operative instruments on a large scale, the two companies will together develop a novel reliable system to enable high-speed label-free cell isolation with high accuracy, which has been difficult to achieve with the existing cell sorting techniques, and to realize stable, low-cost and large-scale production of cells for regenerative medicine and cell therapy.

Hitachi and ThinkCyte will further advance partnerships with pharmaceutical companies and research institutes that have been developing and manufacturing regenerative medicines and cell therapy products in Japan and other countries where demand is expected to be significant, such as North America, in order to make this technology a platform for the production of regenerative medicines and cell therapy products. At the same time, taking advantage of the high-speed digital processing technologies cultivated through the development of information and communication technology by the Hitachi group, Hitachi will integrate this safe and highly reliable instrument in its value chain for regenerative medicine and contribute to the growth of the regenerative medicine and cell therapy industry.

Note:

*1. Cell manufacturing processes, including cultivation, selection, modification, preservation, product quality control, etc.

*2. Chimeric Antigen Receptor T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy.

*3. Division of Regenerative Medicine, Japan Agency for Medical Research and Development, The final report for market research on regenerative medicine and gene therapy (2020).

*4. S, Ota et al., Ghost Cytometry, Science, 360, 1246-1251 (2018).

About the AI-driven cell analysis and cell sorting technologyThinkCyte has developed high-throughput image-based cell sorting technology based on the Ghost Cytometry technology by integrating the principles of advanced imaging technology, machine learning, and microfluidics. By applying structured illumination to cell imaging, structural information of a single cell can be converted to one-dimensional waveforms for high-throughput data analysis. Based on the judgment of a machine-learning (AI) model developed using the waveform data, target cells are isolated in a microfluidic device with high throughput and with minimal damage to the cells.

This data analysis approach eliminates time-consuming image reconstruction processes and allows high-throughput image-based single cell sorting, enabling the discrimination of cells that were previously considered difficult to distinguish by the human eye. Conventional cell sorting methods rely on the use of labels such as cell surface markers for cell sorting; in contrast, ThinkCyte's technology can sort cells without such labels by employing this unique approach. In addition to the field of regenerative medicine and cell therapy, this technology can also revolutionize drug discovery and in vitrodiagnostics fields.

About Hitachi, Ltd.Hitachi, Ltd. (TSE: 6501), headquartered in Tokyo, Japan, is focused on its Social Innovation Business that combines information technology (IT), operational technology (OT) and products. The company's consolidated revenues for fiscal year 2019 (ended March 31, 2020) totaled 8,767.2 billion yen ($80.4 billion), and it employed approximately 301,000 people worldwide. Hitachi drives digital innovation across five sectors - Mobility, Smart Life, Industry, Energy and IT - through Lumada, Hitachi's advanced digital solutions, services, and technologies for turning data into insights to drive digital innovation. Its purpose is to deliver solutions that increase social, environmental and economic value for its customers. For more information on Hitachi, please visit the company's website at https://www.hitachi.com.

About ThinkCyte, Inc.ThinkCyte, headquartered in Tokyo, Japan, is a biotechnology company, which developsinnovative life science research, diagnostics,and treatmentsusingintegrated multidisciplinary technologies, founded in 2016. The company focuses on the research and development of drug discovery, cell therapy, and diagnostic platforms using its proprietary image-based high-throughput cell sorting technology In June 2019, the company was selected for J-Startup by the Ministry of Economy, Trade and Industry of Japan. For more information on ThinkCyte, please visit the company's website at https://thinkcyte.com.

ContactsHitachi, Ltd.Analytical Systems Division, Healthcare Division, Smart Life Business Management Divisionhttps://www8.hitachi.co.jp/inquiry/healthcare/en/general/form.jsp

ThinkCyte, Inc.https://thinkcyte.com/contact

View original content to download multimedia:http://www.prnewswire.com/news-releases/hitachi-and-thinkcyte-announce-collaboration-to-develop-an-ai-driven-cell-analysis-and-sorting-system-301086729.html

SOURCE ThinkCyte, Inc.

Read the rest here:
Hitachi and ThinkCyte announce collaboration to develop an AI-driven cell analysis and sorting system - BioSpace

Challenge trials aren’t the answer to a speedy Covid-19 vaccine – STAT

More than 25,000 people have volunteered so far to be infected with the novel coronavirus through 1DaySooner, an online recruitment organization, as an aid in testing vaccine candidates to prevent Covid-19. These volunteers know that Covid-19 can cause suffering and even death yet they are stepping forward, willing to risk their lives, because some researchers and academics contend that such experiments in humans could accelerate vaccine development.

As a physician and a scientist who has cared for patients and who has been involved in the development of vaccines, I feel the urgency to get a vaccine approved for global use. And I have deep admiration for the courageous volunteers who are willing to put themselves in danger.

In this situation, however, their sacrifice cannot be justified. Volunteers need to be protected from both known and unknown risks. The effort to develop a vaccine should not be jeopardized by this well-intentioned but unnecessary experiment.

advertisement

In the context of an ongoing pandemic, the conventional pace of vaccine development frustrates the public, the government, public health experts, vaccine creators, regulators, and others. It is understandable that many are seeking ways to accelerate the demonstration of safety and efficacy of vaccine candidates. The mumps vaccine, considered the fastest vaccine ever developed, took scientists four years to go from collecting viral samples to securing FDA approval in 1967. A decade or longer is more typical. Everyone is hoping that inventing, testing, obtaining approval and producing a Covid-19 vaccine might be on track to set a new record.

The practice of deliberately infecting people with disease, termed human challenge trials, has a long history. It is embedded in the origin of the very first vaccine in 1796, when Edward Jenner, an English physician, purposely infected his gardeners 8-year-old son with cowpox after observing that people previously infected with cowpox, a relatively mild disease, seemed protected from smallpox, one of the deadliest scourges of the time.

advertisement

Now, in the midst of the coronavirus pandemic, human challenge studies are being considered again.

In the June 1 issue of the Journal of Infectious Diseases, Nir Eyal, Marc Lipsitch, and Peter G. Smith argue that this approach could accelerate the development and approval of a Covid-19 vaccine by many months. That may sound tempting, but human challenge studies with live virus are unlikely to save time. Moreover, there are ethical and practical reasons for not undertaking human challenge studies with this virus. These authors, like 1DaySooners volunteers, are well-intentioned but wrong.

Those in favor of human challenge trials propose enrolling as subjects only healthy young adults, since the Covid-19 mortality rate in this group is low. Just 7% of all Covid-19-related deaths in the U.S. have occurred among those aged 25 to 54 years, compared to 80% in those over age 65. Yet the example of fatal infections in health care workers in the prime of life makes clear that even healthy non-elderly adults may succumb to the novel coronavirus.

Human challenge studies are generally contemplated only when rescue with a lifesaving treatment or intervention is available should a vaccine candidate not protect a volunteer from the disease. But there is no cure or treatment against the SARS-CoV-2 virus that can be deployed with confidence, making viral challenge particularly risky and ethically questionable.

Most people, likely including most of the volunteers, tend to think of vaccines as fully effective: They either work or dont. This belief generally stems from the success of vaccines for childhood diseases like measles and mumps. But some vaccines, especially those for adults, are much less effective: There are seasons when the flu vaccine is only 70% to 80% effective, or sometimes even less. Imagine, for a moment, that a vaccine candidate undergoing testing turns out to generate immunity in 80% of those who receive it. Then 20% will become infected with Covid-19.

An equally disturbing scenario is what if one of the first volunteers dies, either due to the play of chance, a problem with the vaccine, or the individuals genetic makeup? This is unlikely to happen but it can, and did, in another setting with consequences that stretched far beyond the single tragic death.

In 1999, Jesse Gelsinger volunteered for one of the first gene therapy trials. The 18-year-old had a rare metabolic genetic disorder, but his condition was managed with medication; he was basically healthy. He volunteered for a safety trial of a virus-based gene-therapy and died as a result. Missteps in the trial, and the subsequent controversy surrounding his death, set the field of gene therapy back by at least two decades. That hiatus deprived a generation of patients with genetic disorders of treatments.

With vaccines already a target of widespread misinformation campaigns, the death of a single volunteer would likely cause even greater damage. From a public health perspective, it would be especially disastrous if it both slowed the race to develop a coronavirus vaccine and fueled the anti-vaccination movement.

There are other ethical considerations. An important principle in human challenge studies is that subjects must give their informed consent in order to take part. That means they should be provided with all the relevant information about the risk they are considering. But that is impossible for such a new disease.

Covid-19 was initially thought to be mainly a respiratory ailment. We now know that it can damage the kidneys, circulatory system, and the heart. It was initially believed that children could not be sickened by SARS-CoV-2, but it now appears that dozens have developed a severe inflammatory syndrome. And we know nothing about potential long-term complications of Covid-19 because the disease has only been in humans for months. Taken together, this means that no volunteer is able to give true informed consent.

Given these risks, there might still be some justification for a human challenge trial if we knew for certain it would accelerate the development of an effective vaccine. But safer trials can get us to a vaccine in the same amount of time without taking on additional risk for volunteers, especially now that some vaccine candidates already have entered Phase 2 clinical trials and several others are close behind.

In a conventional trial, subjects are injected with either the experimental vaccine or placebo. They are then monitored to see if those who got the vaccine are less likely to contract the disease while going about their daily lives. In a human challenge study, things can theoretically happen more quickly, since volunteers are deliberately infected after getting the trial vaccine or placebo.

But human challenge trials take time, too. For Covid-19, subjects would likely have to receive two doses of vaccine (spaced by weeks), wait for potential immunity to develop, then be infected with the live virus and observed for weeks to months. Since the challenge trial would need to start small and be expanded only with great caution because of the risks involved, it would take months to deliver sufficient data. Safety data, in particular, would be lacking, even though this is one of the biggest issues confronting a new vaccine, because the size of the trial would be too small to garner robust safety data and data about adverse effects of the vaccine would be confounded by the administration of the live virus.

There is no short cut for determining safety.

A large-scale, conventional study could likely be conducted just as quickly. In addition, monitoring and interim analyses of conventional trials raise the possibility of some kind of conditional or emergency use approval while the trials continue. If that happened, a vaccine might be available for certain high-risk or vulnerable groups in record time, namely 12 to 18 months from laboratory to clinic.

A final issue is that the results of the proposed human challenge studies come exclusively from the experience of younger adults, and cannot be extrapolated to the elderly, who tend to have weaker immune responses and the highest Covid-19 mortality rate. The volunteers might end up having risked their own health without truly helping those who are in greatest need of vaccine protection.

The world is overwhelmed by the pandemic. It is imperative to expedite development and approval pathways without forgoing safety and effectiveness. Ascertaining the risks intrinsic to the disease versus those of a new vaccine in specific populations health care workers, first responders, the elderly, those with comorbidities, and the like is essential. But acceleration should not mean forsaking ethical concerns, putting well-intentioned volunteers at needless risk, or setting back global vaccine efforts.

Michael Rosenblatt, M.D., is the chief medical officer of Flagship Pioneering, a venture firm that creates life sciences companies. He is the former chief medical officer of Merck and former dean of Tufts University School of Medicine. He serves as an adviser to Moderna, which is developing a Covid-19 vaccine; he is not a Moderna employee or shareholder. The opinions expressed are his own and do not necessarily reflect those of Flagship Pioneering or Moderna.

View original post here:
Challenge trials aren't the answer to a speedy Covid-19 vaccine - STAT

Sarepta Therapeutics and Selecta Biosciences Enter into Research License and Option Agreement for Selecta’s ImmTOR Immune Tolerance Platform in…

Application of ImmTOR plus Sareptas investigational gene therapies will be evaluated for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophies

CAMBRIDGE, Mass. and WATERTOWN, Mass., June 18, 2020 (GLOBE NEWSWIRE) --Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in precision genetic medicine for rare diseases, and Selecta Biosciences, Inc. (NASDAQ: SELB) today announced that they have entered into a Research License and Option agreement granting Sarepta an option to license the rights to develop and commercialize Selectas immune tolerance platform, ImmTOR, for use in Duchenne muscular dystrophy (DMD) and certain limb-girdle muscular dystrophies (LGMDs). In advance of exercising its option, Sarepta will conduct research and evaluate the utility of ImmTOR to minimize or prevent the formation of neutralizing antibodies (NAb) to adeno-associated virus (AAV) in connection with the administration of Sareptas DMD and LGMD gene therapy candidates.

Sareptas late-stage gene therapy candidates are delivered using AAV in particular, AAVrh74. AAVrh74 was selected because of its safety profile, superior muscle tropism, empirical demonstration of high expression, and low screen-out rate for pre-existing antibodies. Currently, however, all systemic AAV-delivered constructs are one-time therapies that cannot be re-dosed due to the robust post-administration development of NAbs specific to the AAV vector. Selecta is a leader in immune tolerance and has generated strong preclinical evidence to support the potential for re-dosing patients receiving gene therapy.Selecta has reported that in preclinical studies, when used in combination with AAV gene therapy vectors,Selectas ImmTOR immune tolerance platform inhibits the development of NAbs to the vector, permitting re-dosing of the gene therapy. i

As we build our enduring gene therapy engine, we intend not only to rapidly advance treatments for rare, life-ending diseases, but at the same time, to advance the state of genetic medicine science by continually improving the utility of gene therapy. If successful, the ability to re-dose will be an enormous leap forward in the science of gene therapy and provide invaluable benefits to patients beyond those we anticipate with one-time dosing. We are encouraged by the data generated on the ImmTOR platform and excited to join with Selecta to explore the possibility of unlocking the opportunity to safely and effectively re-dose AAV-mediated gene therapies in patients with DMD and LGMDs, if needed, said Doug Ingram, President and Chief Executive Officer, Sarepta Therapeutics.

We are pleased to build on our already strong foundation of strategic partnerships and expand the clinical application of the ImmTOR platform into neuromuscular diseases. The ability to re-dose gene therapy addresses one of the major challenges of one-time therapies today, said Carsten Brunn Ph.D., President and Chief Executive Officer of Selecta Biosciences. We are excited to collaborate with a leader in genetic medicine like Sarepta, and are confident that their expertise in rare diseases combined with our immune tolerance platform has the potential to enhance the long-term therapeutic benefit to patients with these debilitating conditions.

DMD is a rare, degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. LGMDs are a group of over 30 distinct diseases that cause weakness and wasting of the muscles around the hips and shoulders, eventually progressing to the arms and legs. LGMD can be caused by a single gene defect that affects specific proteins within the muscle cell, including those responsible for keeping the muscle membrane intact.

Under the terms of the research license and option agreement, Sarepta will make an initial payment to Selecta, and Selecta is eligible to receive certain pre-clinical milestone fees. If Sarepta exercises its options to enter any commercial license agreements, Selecta will be eligible for additional development, regulatory, and commercial milestone payments, as well as tiered royalties on net product sales. Additional financial details are not being disclosed.

About Selecta Biosciences, Inc.

Selecta Biosciences, Inc. is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its pioneering immune tolerance platform (ImmTOR). Selecta is committed to utilizing ImmTOR to potentially improve the efficacy of biologics, enable re-dosing of life-saving gene therapy, and create novel immunotherapies for autoimmune diseases. Selectas late-stage product candidate, SEL-212, is designed to be a monthly treatment for chronic refractory gout, a debilitating rare disease with a significant unmet medical need. SEL-212 consists of a combination of our ImmTOR platform co-administered with pegadricase, an enzyme designed to treat patients with symptomatic gout, refractory to standard uric acid lowering treatment. Selectas proprietary gene therapy product candidates are in development for certain rare inborn errors of metabolism and incorporate our ImmTOR platform with the goal of addressing barriers to repeat administration. In addition to our own pipeline of core discovery and clinical candidates, Selecta has established collaborative relationships with leading biopharmaceutical companies, including Asklepios BioPharmaceutical (AskBio) for gene therapy, and Swedish Orphan Biovitrum AB (Sobi) for SEL-212. Selecta is based in Watertown, Massachusetts. For more information, please visit http://www.selectabio.com.

Selecta Forward-Looking Statements:

SelectaBiosciences, Inc. (the company), including without limitation, the companys actions regarding the monitoring and assessment of COVID-19 on the companys operations, clinical trials and manufacturing, Sareptas plans to evaluate its gene therapies in combination with the companys ImmTOR technology, the possibility of Sarepta exercising an option to enter into a commercial license agreement, the unique proprietary technology platform of the company and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the ability of the companys ImmTOR platform to unlock the full potential of biologic therapies, the potential treatment applications for product candidates utilizing the ImmTOR platform in areas such as enzyme therapy and gene therapy, the novelty of treatment paradigms that Sarepta is able to develop in combination with the companys ImmTOR technology, the potential of any therapies developed by Sarepta in combination with the companys ImmTOR technology to fulfill unmet medical needs, the companys plan to apply its ImmTOR technology platform to a range of biologics for rare and serious diseases, the ability of Sareptas existing therapies to target the heart and skeletal muscle, expected payments to be made to the company under the Research License and Option Agreement, the potential of the ImmTOR technology platform generally and the companys ability to grow its strategic partnerships, the sufficiency of the companys cash, cash equivalents and short-term investments, and other statements containing the words anticipate, believe, continue, could, estimate, expect, hypothesize, intend, may, plan, potential, predict, project, should, target, would, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including their uncertain outcomes, the effect of the COVID-19 outbreak on any of the companys planned or ongoing clinical trials, manufacturing activities, supply chain and operations, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, the unproven approach of the companys ImmTOR technology, Sareptas ability to research and develop therapeutic candidates using the companys ImmTOR technology, undesirable side effects of the companys product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials as well as the impact of the COVID-19 outbreak on those third parties and their ability to continue their operations, the companys inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, managements ability to perform as expected, potential delays in regulatory approvals, Sareptas ability to make up-front and milestone payments, the companys business development strategy, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the companys recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock including stock market fluctuations that occur as a result of the COVID-19 outbreak, and other important factors discussed in the Risk Factors section of the companys most recent Quarterly Report on Form 10-Q, and in other filings that the company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the companys views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The company specifically disclaims any intention to update any forward-looking statements included in this press release.

AboutSarepta Therapeutics

At Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.comor follow us onTwitter,LinkedIn,InstagramandFacebook.

Sarepta Forward-Looking Statement

This press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding the parties undertakings under the agreement and potential payments and fees; the potential benefits of Sareptas gene therapy product candidates; the potential of ImmTOR to enable re-dosing of AAV gene therapy; Sareptas intention to rapidly advance treatments for rare, life-ending diseases, and to advance the state of the genetic medicine science by continually improving the utility of gene therapy; the potential of re-dosing to provide invaluable benefits to patients beyond those Sarepta anticipates with one-time dosing;the possibility of unlocking the opportunity to safely and effectively re-dose AAV-mediated gene therapies in patients with DMD and LGMDs, if needed; and the potential of the collaboration between Sarepta and Selecta to enhance the long-term therapeutic benefit to patients with these debilitating conditions.

These forward-looking statements involve risks and uncertainties, many of which are beyond our control. Known risk factors include, among others: the expected benefits and opportunities related to the collaboration between Sarepta and Selecta may not be realized or may take longer to realize than expected due to challenges and uncertainties inherent in product research and development. In particular, the collaboration may not result in any viable treatments suitable for commercialization due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement; success in preclinical trials does not ensure that later clinical trials will be successful; Sarepta may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans, and bringing its product candidates to market, due to a variety of reasons, many of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates and the COVID-19 pandemic; and even if Sareptas programs result in new commercialized products, Sarepta may not achieve the expected revenues from the sale of such products; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2019, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by Sarepta which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect Sareptas business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Selecta Contacts:For Media:Joshua R. MansbachSolebury Trout+1-646-378-2964jmansbach@soleburytrout.com

For Investors:Lee M. SternSolebury Trout+1-646-378-2922lstern@soleburytrout.com

Sarepta Contacts: Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

_____________________________iNature Communications,October 2018.

Go here to see the original:
Sarepta Therapeutics and Selecta Biosciences Enter into Research License and Option Agreement for Selecta's ImmTOR Immune Tolerance Platform in...

AI Applications for COVID-19 Research and Other News – Bio-IT World

May 22, 2020 |A pair of studies demonstrate antibody responses to COVID-19 in primates. Researchers are applying artificial intelligence to lung images of COVID-19 patients. An accurate, easy-to-use, fully disposable, rapid and handheld test that consumers and healthcare providers in clinics can use to detect active SARS-CoV-2. We round up the weeks research and industry news for COVID-19.

Literature Updates

A pair of studies led by researchers at Beth Israel Deaconess Medical Center(BIDMC) were published in the journal Science. In the first study, the team demonstrated that six candidate DNA vaccines induced neutralizing antibody responsesand protected against SARS-CoV-2 in rhesus macaques. DOI: 10.1126/science.abc6284. In the second study, the team demonstrated that macaques that recovered from COVID-19 developed natural protective immunity against re-infection. Upon second exposure, the animals demonstrated near-complete protection against the virus. These data suggest natural protective immunity against COVID-19 in this model. DOI: 10.1126/science.abc4776.

Insilico Medicinehas co-authored a preprint paper with Nanome.aidescribing 10 potential small molecule inhibitors targeting the SARS-CoV-2 main protease that were generated by artificial intelligence (AI). The approach taken, called AI imagination, involves teaching a computer what the target protein looks like, letting it sniff out the binding pockets, and then imagine molecules with certain features having to do with the likelihood that a molecule will fit inside, and stay inside, a binding pocket. The AI-generated molecules are some of the first non-covalent drug candidates for COVID-19; non-covalent inhibitors are safer and more selective than covalent inhibitors. DOI: 10.13140/RG.2.2.13846.98881.

Researchers from the La Jolla Institute for Immunologyhave published the first cellular immunology data to help guide social distancing recommendations. Published in Cell, the study documents a robust antiviral immune response to SARS-CoV-2 in a group of 20 adults who had recovered from COVID-19. The findings show that the body's immune system is able to recognize SARS-CoV-2 in many ways, dispelling fears that the virus may elude ongoing efforts to create an effective vaccine. DOI: 10.1016/j.cell.2020.05.015.

Previous data from COVID-19 patients suggests that cigarette smokers are more likely to have health complications. One possible reason, researchers report in Developmental Cell, is that smoking increases the gene expression of ACE2the protein that binds SARS-CoV-2which may promote COVID-19 infection. The study suggests that prolonged smoking could cause an increase of the ACE2 protein in the lungs, possibly resulting in a higher rate of morbidity in patients. ACE2, or Angiotensin Converting Enzyme 2, is a regulatory protein that has been linked to vulnerability to the 2003 SARS (2003) virus. DOI: 10.1016/j.devcel.2020.05.

Researchers from the University of Trentohave published a novel fully-annotated dataset of lung ultrasonography (LUS) imagesfrom COVID-19 patients collected from several Italian hospitals, with labels indicating the degree of disease severity at a frame-level, video-level, and pixel-level (segmentation masks). Leveraging these data, they introduce a novel deep network, derived from Spatial Transformer Networks, which simultaneously predicts the disease severity score associated to an input frame and provides localization of pathological artefacts in a weakly-supervised way. They also benchmark state of the art deep models for estimating pixel-level segmentations of COVID-19 imaging biomarkers. Results were published in IEEE Transactions on Medical Imaging(Early Access). DOI: 10.1109/TMI.2020.2994459.

Leading immunologists in Japan reviewed two recent studies by Zhou et al. and Hoffmann et al. in order to understand their implications for finding effective therapeutic strategies for ARDSin COVID-19 patients. Based on their review, they are proposing a possible molecular mechanism that causes the massive release of proinflammatory cytokines, or a cytokine storm, that leads to acute respiratory distress syndrome (ARDS) in COVID-19 patients. Their suggestions are published in the journal Immunity. DOI: 10.1016/j.immuni.2020.04.003.

Mount Sinairesearchers are also applying artificial intelligence to lung images of COVID-19 patients. The Mount Sinai team has developed an algorithm that can rapidly detect COVID-19 based on how lung disease looks in computed tomography (CT scans) of the chest, in combination with patient information including symptoms, age, bloodwork, and possible contact with someone infected with the virus. This study, published in Nature Medicine, could help hospitals across the world quickly detect the virus, isolate patients, and prevent it from spreading during this pandemic. DOI: 10.1038/s41591-020-0931-3.

Patients infected with either severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 produce antibodies that bind to the other coronavirus, but the cross-reactive antibodies are not cross protective, at least in cell-culture experiments, researchers report in Cell Reports. Researchers analyzed blood samples collected from 15 SARS-CoV-2-infected patients in Hong Kong between 2 and 22 days after the onset of symptoms. Compared to blood samples from healthy controls, the five samples collected from patients 11 days after symptom onset or later had antibodies capable of binding to the RBD and other parts of the S protein on both SARS-CoV-2 and SARS-CoV. The researchers also analyzed blood samples collected from seven patients 3 to 6 months after infection with SARS-CoV. Compared to blood samples from healthy controls, those collected from patients had antibodies capable of binding to the RBD and other parts of the S protein on SARS-CoV-2. It remains unclear whether such antibodies offer cross protection in the human body or potentiate disease. DOI: 10.1016/j.celrep.2020.

An antibody called S309, first identified in a blood sample from a patient who recovered from Severe Acute Respiratory Syndrome in 2003, inhibits related coronaviruses, including SARS-CoV-2. The findings have been accepted for publication in Natureand the antibody is now on a fast-track development and testing path at Vir Biotechnology. It has not yet been shown to be protective in living systems. The S309 antibody is particularly potent at targeting and disabling the spike protein that promotes the coronavirus entry into cells. It was able to neutralize SARS CoV-2 by engaging with a section of the spike protein nearby the attachment site to the host cell. DOI: 10.1038/s41586-020-2349-y.

Industry Updates

Illuminaand the Illumina Corporate Foundation have committed more than $10M to COVID-19-related research and support. To support public health efforts associated with SARS-CoV-2 surveillance, sequencing and monitoring, Illumina is providing in kind donations valued at approximately $5M dollars for instruments and consumables. In addition, we dedicated more than $2M to COVID-19-related research efforts. To advance scientific research, Illumina, Inc. recently released the SARS-CoV-2 Data Toolkit, making it easier for researchers to detect and identify the viral sequence in their samples and contribute their findings to critical public databases. The toolkit is freely accessible on BaseSpace Sequence Hub until October 2020. Finally, the Illumina Foundation has awarded more than $3M in philanthropic donations, of which $1M has gone to the CDC Foundation COVID Emergency Response Fund, and $2M to local community-based initiatives in the areas where we operate. Press release.

Mammoth Biosciences and GSK Consumer Healthcareare collaborating to develop an accurate, easy-to-use, fully disposable, rapid and handheld testthat consumers and healthcare providers in clinics can use to detect active SARS-CoV-2. The collaboration will use Mammoth Biosciences CRISPR-based DETECTR platform that can identify and signal the presence of viral RNA strands obtained through a simple nasal swab. The test, which has the potential to deliver point-of-use results in less than 20 minutes, will be available first in the clinical setting and ultimately by consumers at home. Press release.

iSpecimenis partnering with myOnsite HealthCareto offer mobile phlebotomysupport that will bring convenient, at-home sample collection to patients and donors interested in advancing research who would otherwise have limited ability to participate. The mobile service extends iSpecimens ongoing mission to advance medical research by efficiently connecting researchers with patients, biospecimens, and the data they need to perform their important work. It also expands the companys recent initiatives to identify, collect, aggregate, manage, and ship specimens from COVID-19 patients. Press release.

Read more:
AI Applications for COVID-19 Research and Other News - Bio-IT World

UBC scientist identifies a gene that controls thinness – UBC Faculty of Medicine – UBC Faculty of Medicine

Why can some people eat as much as they want, and still stay thin?

In a study published today in the journal Cell, Life Sciences Institute Director Dr. Josef Penninger and a team of international colleagues report their discovery that a gene called ALK (Anaplastic Lymphoma Kinase) plays a role in resisting weight gain.

We all know these people, who can eat whatever they want, they dont exercise, but they just dont gain weight. They make up around one per cent of the population, says senior author Penninger, professor in the Faculty of Medicines department of medical genetics and a Canada 150 research chair.

Dr. Josef Penninger

We wanted to understand why, adds Penninger. Most researchers study obesity and the genetics of obesity. We just turned it around and studied thinness, thereby starting a new field of research.

Using biobank data from Estonia, Penningers team, including researchers from Switzerland, Austria, and Australia, compared the genetic makeup and clinical profiles of 47,102 healthy thin, and normal-weight individuals aged 20-44. Among the genetic variations the team discovered in the thin group was a mutation in the ALK gene.

ALKs role in human physiology has been largely unclear. The gene is known to mutate frequently in several types of cancer, and has been identified as a driver of tumour development.

Our work reveals that ALK acts in the brain, where it regulates metabolism by integrating and controlling energy expenditure, says Michael Orthofer, the studys lead author and a postdoctoral fellow at the Institute of Molecular Biology in Vienna.

When Penningers team deleted the ALK gene in flies and mice, both were resistant to diet-induced obesity. Despite consuming the same diet and having the same activity level, mice without ALK weighed less and had less body fat.

As ALK is highly expressed in the brain, its potential role in weight gain resistance make it an attractive mark for scientists developing therapeutics for obesity.

The team will next focus on understanding how neurons that express ALK regulate the brain at a molecular level, and determining how ALK balances metabolism to promote thinness. Validating the results in additional, more diverse human population studies will also be important.

Its possible that we could reduce ALK function to see if we did stay skinny, says Penninger. ALK inhibitors are used in cancer treatments already, so we know that ALK can be targeted therapeutically.

The study was supported by the Estonian Research Council, the European Union Horizon 2020 fund, and European Regional Development Fund, the von Zastrow Foundation, and the Canada 150 Research Chairs Program.

See original here:
UBC scientist identifies a gene that controls thinness - UBC Faculty of Medicine - UBC Faculty of Medicine

Gene therapy: The ‘next generation’ of medicine – Irish Medical Times

For people with rare diseases, a single gene therapy treatment could restore normal function and alleviate the burden of ongoing care, as Dr Ian Winburn tells Kennas Fitzsimons

Dr Ian Winburn

Gene therapy is the next generation of medicine that targets the underlying cause of genetic diseases. It has the potential to offer patients a really transformational clinical benefit and improve quality of life.

Thats according to Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and Inborn Errors of Metabolism (IEM), Rare Diseases, Pfizer Biopharmaceuticals Group. Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and IEM, Pfizer Biopharmaceuticals Group, pictured right during his presentation on gene therapy at BioPharma Ambition held in Dublin Castle on March 4. Pic: Conor McCabe Photography.

Formerly a clinician in the UK National Health Service (NHS), Dr Winburn trained in general surgery and completed a PhD on novel drug discovery in renal transplantation before moving into industry 10 years ago, where he worked in the area of inflammation and immunology before leading the European haemophilia team.

Dr Winburn is now working to develop innovative gene therapies with the potential to restore normal function to patients with rare diseases, possibly with just a single treatment, changing the way people manage their disease.

Gene therapy: What is it?Gene therapy uses genes as medicine. It works by introducing functioning copies of missing or defective genes into the body and can target the underlying cause of a disease at the cellular level.

There are various types of gene therapies, such as the gene editing technique, CRISPR (clustered regularly interspaced short palindromic repeats), as well as epigenetic approaches that look at ways in which genes may be turned on or turned off.

Pfizer Rare Disease is focusing on an in-vivo approach that utilises a recombinant adeno-associated virus (AAV) to deliver the gene therapy.

This approach works by targeting the missing or non-functional gene in an individuals DNA and adding a copy of it with a functioning gene that, in turn, produces a functioning protein.

The functioning gene serves as a blueprint for the tissue to create the missing or non-functioning protein that is causing a disease.

Dr Winburn said: Gene therapy is in the branch of genetic medicine, where you can think about approaches that look to add a gene to a host cell, and that gene goes on and codes for a protein. That protein its coding for can replace a missing protein. So, in the example of haemophilia, where theres a missing factor VIII or factor IX clotting factor, that protein that is either missing or is faulty could be essentially administered through a gene therapy. A gene is added to a host cell that codes for the factor VIII or factor IX and therefore replaces that protein.

The functioning gene is delivered directly to the targeted cells by means of a highly specialised viral vector. This vector, effectively, is the package that contains the gene. In simple terms, it can be likened to the cardboard boxes that online retailers use to ship products.

The manufactured vectors are protein shells modelled after viruses in which all infectious viral components have been removed, and a functioning gene is added. Different viral vectors are used to reach specific tissues in the body, such as the liver or muscle.

VectorVector is a great word because vector describes a direction, by definition, and the other way we can think about vector is a vector often carries something. There are a few approaches you can use to develop a vector. We have embraced an AAV vector that has the capacity to deliver the transgene, the gene that is going to be added to the host somatic cell. In the case of haemophilia, it is targeted at the liver, Dr Winburn says.

Rare diseases focusAbout 280 million people worldwide live with a genetic disease, and more than 80 per cent of rare diseases are genetic in origin, according to Pfizer. For people born with rare diseases, the burden of disease management can be huge. Treatment is often ongoing and may be lifelong. Gene therapy could enable patients to live without the need for ongoing treatment. This raises the prospect of relief not only from symptoms but also from the burden of disease management.

Dr Winburn elaborates on the reasons why gene therapy approaches are currently focused specifically on rare diseases that have single-gene alterations.

It tends to be rare genetic diseases that are monogenic in nature Some of the more common diseases are very much multifactorial in origin: there may be a genetic component but there are other aspects to their aetiology rather than these single, monogenic conditions that gene therapy really lends itself to.

The other aspect is that these are areas of huge unmet medical need. Often, there isnt a high standard of care with either medicines or clinical interventions that are ultimately influencing the progression and the symptoms of the disease, he says.

A lot of rare diseases often affect children by the very nature of their being of genetic origin. In some cases, children dont get the opportunity to grow up into adulthood because of these rare diseases. Having the opportunity to develop medicines where there is such a high level of unmet need and, ultimately, impact in a positive way the lives of families and their carers is a huge motivation.

Dr Winburn adds that rare diseases, collectively, are common. There are approximately 7,000 rare diseases, and the majority of these are of genetic origin. Gene therapy offers a groundbreaking technology to address these genetic diseases that have historically not had particularly strong standards of care or clinical treatment paradigms offered to them.

Gene therapy for haemophiliaPeople with the genetic disorder of haemophilia have insufficient levels of a clotting factor that helps to stop bleeding. Consequently, they bleed for longer than other people. The disease is typically treated through infusions of the missing clotting factor, with patients undergoing regular replacement therapy. Gene therapy could revolutionise this treatment model.

Its really important to put yourself in the position of a parent who has a young child who has haemophilia, Dr Winburn says.

Often, this disorder of coagulation that results in spontaneous bleeding due to the lack of functioning clotting factor first presents as early as the age of two, classically when children are becoming toddlers, when they start bumping into things and they develop bruising and the likes.

That alerts their parents attention to the possibility that there is something wrong with their clotting system and they [undergo] clinical tests and a diagnosis is made. Or, because its a genetic condition, it may run in families and parents are aware of the possibility of their newborn having haemophilia.

But if you are diagnosed, for example, at the age of two, it means that the mainstay of treatment is factor replacement. So, that commonly is an intravenous infusion possibly two to three times a week, possibly once a week, or once every other week, depending on whether its haemophilia A or B and what type of medicine is being prescribed. But its certainly frequent treatments. Again, if you put that back to a parent wholl be doing those infusions from the age of two or three that lifelong need and burden is huge.

While factor replacement enables children to live a full and active life to a degree, children with haemophilia may not necessarily get the opportunity to engage in all the activities children typically partake in as they are growing up, such as contact sports, Dr Winburn says.

There is this ongoing, lifelong burden of treatment. As those boys transition into adulthood, they often take responsibility for that and if they dont get their treatment then they will bleed spontaneously into their joints, they get problems with haemarthropathy, causing damage.

Ultimately, the incidence of joint damage and joint replacement surgeries is incredibly significant in the haemophilia population. And that is often despite optimal prophylaxis, where its being prescribed.

So, when you think about gene therapy, this is a single, one-off treatment with the potential to alleviate the need for regular infusion for a patient.

Not all patients will be eligible for a gene therapy or are being studied in gene therapy trials. This is not going to be something thats available for everybody. But for those that are eligible, and ultimately in disease where a gene therapy has been licensed by the regulator, this really does have the potential to massively impact their lives and give them a sense of normality that they havent necessarily had up until that point in time.

Future expectationsWhile gene therapy holds promise for many people with genetic diseases, it will not be an appropriate solution for every patient. The potential risks and benefits of gene therapy will be fully established through clinical trial programmes and with continued research and evaluation.

Patient safety and suitability are always primary considerations in the development of new treatments as they progress from preclinical and clinical testing through regulatory approval to potential commercial distribution. Dr Winburn stresses that, as regards the development of new gene therapies, patient safety is paramount.

Safety is always at the forefront of our thinking, it is the heart of our clinical trial programmes, it is the heart of all our regulatory work.

It is an ongoing process around evaluating safety, and particularly long-term safety, and there is a critical importance for all patients that ultimately receive a gene therapy to be followed up long-term within registries, within clinical databases, so that we can monitor and evaluate long-term safety. All our trials are designed so that safety outcomes are critically part of it and its something that we are ever watchful of.

For some patients, gene therapy is already a reality. There are currently a few rare diseases for which gene therapies are available as therapeutic options in Europe, and Dr Winburn anticipates that there may be up to 30 approved by 2023.

There is a rare congenital cause of blindness that currently has a gene therapy available and similarly a rare neurological condition that affects children also has a gene therapy available, thats spinal muscular atrophy (SMA). There is also a gene therapy for beta thalassaemia that has recently been approved and is available within Europe. In terms of haemophilia, the first gene therapy is currently under review in Europe.

It may be premature to imagine a scenario whereby gene therapy is used to treat chronic diseases more generally, but in terms of future applications for these emerging technologies it is a case of watch this space.

This is an area where we are definitely in breakthrough technology. At this moment in time, our focus has been on rare diseases. There is, of course, an interest in understanding what is possible with gene therapy in terms of where it could be utilised, Dr Winburn says.

I dont want to provide any false hopes, but I think aspirationally, there is a hope that this could certainly impact many patients and their families in a positive way.

In association with Pfizer Biopharmaceuticals Group.

Continued here:
Gene therapy: The 'next generation' of medicine - Irish Medical Times

Novartis wins conditional EU approval for gene therapy Zolgensma – Reuters

FILE PHOTO: The logo of Swiss drugmaker Novartis is pictured at the French company's headquarters in Rueil-Malmaison near Paris, France, April 22, 2020. REUTERS/Charles Platiau

ZURICH (Reuters) - Novartis won European approval for its gene therapy Zolgensma for the hereditary disease spinal muscular atrophy (SMA), the Swiss drugmaker said on Tuesday, adding it is in talks over price with countries in hopes of a quick launch.

The European Commission gave conditional approval to the therapy, whose U.S. price is $2.1 million, for patients with a clinical diagnosis of SMA Type 1, the most severe form of the disease, or SMA patients with up to three copies of a specific gene that helps doctors predict how severe the disease will be.

The EU approval covers babies and young children with SMA up to 21 kilograms. The medicine also has approval in Japan.

Novartis got Zolgensma with its $8.7 billion takeover of U.S.-based AveXis in 2018 and has forecast more than $1 billion in sales for the treatment, which in trials has been shown to significantly improve survival and motor function of babies with SMA, in particular those treated before symptoms develop.

Novartis said it is in talks with nations over what it calls its Day One access program, which the Basel-based drugmaker said is aimed at speeding up treatment by dealing with payment issues up front, even before national pricing and reimbursement agreements with individual countries are in place.

The Day One access program ensures the cost of patients treated before national pricing and reimbursement agreements are in place align with the value-based prices negotiated following clinical and economic assessments, Novartis said, adding the medicine will be immediately available in France.

Drug pricing in Europe varies from country to country, often relying on individual negotiations with regulators and pricing watchdogs that can slow down access, including in instances where officials conclude companies are seeking too much money for their medicines relative to the value they bring.

Reporting by John Miller; editing by Thomas Seythal and Brenna Hughes Neghaiwi

Read the original here:
Novartis wins conditional EU approval for gene therapy Zolgensma - Reuters

Are we wired for romance? – University of California

If youve ever been a newlywed, you know the tingly euphoria of saying I do and starting a life with your spouse. This is romantic love, Western style. We often chalk it up to chemistry, an ill-defined connection of hearts and minds. Groundbreaking research at UC Santa Barbara finds we were closer than we knew.

For the first time, researchers have explored the neural and genetic connections to romantic love in newlyweds. By using functional magnetic resonance imaging (fMRI) and genetic analysis of 19 first-time newlyweds, Bianca Acevedo and her collaborators showed that romantic love maintenance is part of a broad mammalian strategy for reproduction and long-term attachment that is influenced by basic reward circuitry, complex cognitive processes and genetic factors.

In short, were hard-wired to sustain romantic love to maintain a successful marriage and the family unit, thanks to neurotransmitters like dopamine and a suite of genetic mutations.

This is the first study to examine the neural and genetic correlates of romantic love maintenance, said Acevedo, a research scientist at UC Santa Barbaras Department of Psychological & Brain Sciences and the lead author of After the Honeymoon: Neural and Genetic Correlates of Romantic Love in Newlywed Marriages in the journal Frontiers in Psychology.

The study showed that the maintenance of love is not only associated with activation of subcortical regions but also higher order centers of the brain, she said. Also, for the first time we provide evidence that the propensity to sustain romantic love may be affected by genetic variability. Specifically, the genes we examined are associated with pair-bonding behaviors including fidelity and sexual behaviors; and social behaviors such as trust, eye-gazing and attachment.

To test their hypothesis that romantic love is a developed form of the mammalian drive to find and keep mates, the researchers performed fMRI scans of the brains of the members of the study group 11 women and eight men. Participants were shown alternating images of their partners and a neutral acquaintance they knew well.

At the start of each session, the subjects were instructed to recall non-sexual events with the person whose face was displayed. While still in the scanner, participants rated their moods to verify that the evoked emotions corresponded to the target image.

The participants were tested around the time of marriage and a year later.

In addition, they provided saliva samples for testing of vasopressin, oxytocin and dopamine genes implicated in pair bonding in non-human mammals, such as voles.

Our findings showed robust evidence of the dopamine reward systems involvement in romantic love, Acevedo said. This system is interesting because it is implicated in motivation, energy, working for rewards, and is associated with corresponding emotions such as excitement, euphoria and energy, as well as frustration if the drive is thwarted.

Acevedos current research builds on her work on empathy and altruism and its correlates in the brain.

Empathy has its roots in social bonding, she explained. In our previous work we showed that although humans express sentiments such as empathy and altruism towards strangers and non-close others, brain responses to partners are stronger. Thus, there is specificity. Romantic love is somewhat different in that it may or may not include empathy or altruism, but in healthy partnerships it does.

For some romantics, it might seem a tad clinical to chalk up our feelings of love and commitment to biochemistry. Acevedo, however, said gene mutations and brain activity are only components of romance and belonging.

Humans are creative and clever, she said. Romantic love inspires people to know how to put a smile on their partners face. By making our partners happy we not only keep our relationships stable, but we also derive joy from such events.

In the brain, Acevedo continued, this is shown as increased reward activation when people are shown images of a partner smiling and they are told that something wonderful has happened to the partner. People know this intuitively. They know that romance goes a long way in finding and keeping a preferred mate. Thats why there is multibillion-dollar industry built on it from dating sites, to lingerie to Hallmark cards, chocolate and diamond rings.

And besides, our chemical impulses dont buy flowers or cook dinner.

Love is basic but complex, Acevedo said. We are wired to love, but it takes work to find and keep love alive."

Nancy L. Collins, a professor in UC Santa Barbaras Psychological and Brain Sciences, was a co-author of After the Honeymoon. She is also director of the UC Santa Barbara Close Relationship Lab. Other authors are Michael J. Poulin of the University of Buffalo and Lucy L. Brown of the Albert Einstein College of Medicine in New York.

See the original post here:
Are we wired for romance? - University of California

Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 – GlobeNewswire

CAMBRIDGE, Mass., April 29, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report first quarter 2020 financial results after the Nasdaq Global Market closes on Wednesday, May 6, 2020. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its first quarter 2020 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 2553748. Please specify to the operator that you would like to join the "Sarepta First Quarter 2020 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

View original post here:
Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 - GlobeNewswire

Vertex Receives European CHMP Positive Opinion for KALYDECO (ivacaftor) for Children and Adolescents With Cystic Fibrosis Between the Ages 6 Months…

LONDON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the European Medicines Agencys (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the label extension of KALYDECO (ivacaftor), to include the treatment of children and adolescents with cystic fibrosis (CF), ages 6 months and older weighing at least 5 kg who have the R117H mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Todays announcement is important for young people with CF, as early intervention and treatment of this devastating and progressive disease is key to keeping patients healthier longer, said Carmen Bozic, M.D., Executive Vice President and Chief Medical Officer at Vertex. This milestone also brings us one step closer to achieving our ultimate goal of bringing medicines forward to all people with CF.

The European Commission will now review the CHMPs positive opinion, and should they issue a favorable adoption, KALYDECO (ivacaftor) will be the first and only approved medicine in Europe to treat the underlying cause of CF in patients ages 6 months and older with the R117H mutation. In countries where long-term reimbursement agreements have been secured, KALYDECO (ivacaftor), if approved, would be available to eligible patients shortly after Marketing Authorization. In Germany, the medicine would be available at Marketing Authorization. In all other countries, we will work closely with relevant authorities in Europe to secure access for eligible patients quickly.

In Europe, KALYDECO (ivacaftor) is already approved for the treatment of people with CF ages 18 and older with the R117H mutation, and children ages 6 months and older weighing at least 5 kg who have one of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people worldwide. CF is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF. While there are many different types of CFTR mutations that can cause the disease, the vast majority of all people with CF have at least one F508del mutation. These mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working and/or too few CFTR proteins at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

About KALYDECO (ivacaftor)

Ivacaftor is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, ivacaftor is an oral medicine designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London, UK. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 10 consecutive years on Science magazine's Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Bozics statements in the second paragraph of this press release, and statements regarding our expectations for the approval and availability of KALYDECO in Europe, and our plans for securing access to KALYDECO for eligible patients in Europe. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, risks related to obtaining and commercializing KALYDECO in Europe, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

View source version on businesswire.com: https://www.businesswire.com/news/home/20200501005167/en/

Read this article:
Vertex Receives European CHMP Positive Opinion for KALYDECO (ivacaftor) for Children and Adolescents With Cystic Fibrosis Between the Ages 6 Months...

Headaches After Exercise? Its Linked to Your Intensity, New Research Suggests – runnersworld.com

If youre prone to migraines, you may have heard that exercise can decrease their frequency and improve their symptoms, based on previous research about how activity can reduce migraine triggers. But a recent study in Clinical Chemistry and Laboratory Medicine adds an important caveat to that advice: Watch your intensity.

Researchers looked at 48 male amateur runners, who ran a half-marathon distance at 75 to 85 percent of maximal oxygen uptakea measure of their running intensity.

Before and after running, participants had blood drawn to determine their levels of calcitonin gene-related peptide (CGRP), a compound in your body responsible for triggering physical reactions like vasodilationdilation of your blood vessels, which increases blood pressureand inflammation in your nervous system. CGRP levels is often associated with headache pain, especially migraines.

The concentration of the compound was significantly increased in the entire group, and those who were prone to headaches reported suffering from one after the run. That led researchers to conclude that medium-distance endurance exercise is a booster for CGRP, and that high-intensity exercise can heighten that reaction even morepotentially triggering both migraines and headaches brought on by exertion.

Does that mean if youre a headache sufferer, you need to find a different activity? Thankfully, no. But you may need to dial back the intensity in your running, study author Fabian Sanchis-Gomar, M.D., Ph.D., of the Division of Cardiovascular Medicine at Stanford University Medical Center told Runners World. Low-to-moderate exercise doesnt seem to be as much of a trigger, he said.

[Run faster, stronger, and longer with this 360-degree training program.]

If thats not an option, he suggested talking with a doctor about migraine preventive therapy, since that often involves medication that blocks the CGRP receptor specifically. Although this study didnt cover whether runners on that medication would still get migraines, Sanchis-Gomar suggested that its likely they wouldnt, because even though the CGRP would surge, the receptors would block it enough to reduce the risk of headache pain.

For those who arent prone to migraines, though, keep on trucking: CGRP increases are actually a good thing for you.

High-intensity exercise represents an insult [interruption of blood flow] for the cardiovascular system: increasing blood pressure, said Sanchis-Gomar. CGRP counteracts this and has a protective effect for cardiovascular function.

See the article here:
Headaches After Exercise? Its Linked to Your Intensity, New Research Suggests - runnersworld.com

UW researchers collaborate with New York doctors for improved COVID-19 treatments – The Badger Herald

The Albany Medical Center in New York and University of Wisconsin researchers are collaborating to find a way to better allocate medical resources to COVID-19 patients using mass spectrometry techniques.

According to a UW press release, Dr. Ariel Jaitovich, a pulmonary and critical care physician at the Albany Medical Center, reached out to UW researchers for improving treatment and care for COVID-19 patients.

Its a new disease. Two months ago, we knew nothing about it, Dr. Jaitovich said in the release. What we are trying to do now is do systematic work to better understand what this disease is about.

UW researchers create survey to understand community beliefs, behaviors amid COVID-19 pandemicWith the help of the League of Wisconsin Municipalities, University of Wisconsin released a research survey tracking peoples current behaviors Read

The team is comprised of the Albany Medical Center in New York, Morgridge Institute for Research and the Department of Biomolecular Chemistry at the UW School of Medicine and Public Health, according to the release.

SMPH professor Josh Coon, who specializes in mass spectrometry research, is working together with the research group to contrast samples from COVID-19 patients with control samples of those who have tested negative for the virus. The team will analyze about 150 samples from the Albany Medical Center to understand the molecular profile of COVID-19, according to the press release.

UW professionals discussed transmission of, responses to COVID-19 through online panelAs part of the Crossroads of Ideas lecture series, UW professionals discussed transmission of and responses to COVID-19 on Tuesday, Read

This is extremely important for many reasons, because you can, for example, intervene early with people who are more likely to do worse over time based on these early identified markers, Coon said inthe release. You can better allocate resources in a moment in which there is a shortage of resources to deal with this pandemic.

Coon said mass spectrometry can provide molecular signals that can then help in distinguishing between mild and severe cases. Coon also said some possible indicators of the severity of the disease could be blood clotting factors in lung vessels and cytokine storms that trigger the immune systems inflammatory response to skyrocket and result in acute respiratory distress syndrome, according to the release.

UW research team analyzes travel, social media data to monitor COVID-19 spreadA multidisciplinary research team, headed by University of Wisconsin professor Song Gao, started analyzing travel and social media data to Read

The Coon Laboratory is investigating the molecular signals of the disease and Jaitovichs team in New York is examining the potential genetic influences on COVID-19 through RNA sequencing by collaborating with Associate Director of Bioinformatics Ron Stewart and computational biologist Scott Swanson at the Morgridge Institute for Research.

We should be able to get an idea about what genes or gene sets are involved in things like inflammation, and how that might differ between COVID-19 and other ARDS cases, Stewart said in the release.

Excerpt from:
UW researchers collaborate with New York doctors for improved COVID-19 treatments - The Badger Herald

One-of-a-Kind Coronavirus Was Artificially Produced? – The Liberty Web English

Interview

We asked a U.S. expert, specialized in poison and biochemistry, about the origin and motive behind the coronavirus. His books include Overall View of Chemical and Biological Weapons published in 2001.

Colorado State UniversityProfessor Emeritus

Dr. Anthony Tu

Born in Taipei in 1930. After graduating from National Taiwan University under Japanese rule, Tu studied biochemistry at the University of Notre Dame, Stanford University and Yale University.

I believe theres a high possibility that the Wuhan virus was created artificially. I rule out the theory that the coronavirus was originated naturally because a bat-borne virus doesnt transfer naturally to other people.

Shi Zhenglis research team at the Wuhan Institute of Virology of the Chinese Academy of Sciences in Wuhan has been researching the transmission of bat-borne SARS viruses across species. In November 2015, five years before the coronavirus pandemic, she published in Nature Medicine (*1) about her successful experiment of manipulating the SARS virus to have harmful effects on mice respirators.

Although the Wuhan virus is based on the bat-borne SARS virus, the genetic sequence is slightly different than that of SARS. Research done by Professor Pradhan of India have found that the HIV and the Wuhan virus have similar protuberances. The coronavirus has been developed to infect people easier by artificially inserting four HIV-derived gene sequences into the genetic sequence of the SARS virus.

In terms of their research motive, it certainly could be for vaccine development. However, it is unnatural to develop a vaccine for a virus that is not widespread. Another speculation in the U.S. is the biological weapons theory. Although there remains uncertainty since Chinas hasnt confessed, we can naturally assume from research articles that the Wuhan virus was developed as a biological weapon and the artificially-developed coronavirus was accidentally leaked from their research facility.

Dr. Shis paper also suggested an application on primates. At the time, this led to heated debates in Europe and the U.S. French researchers warned that if the virus escapes, nobody could predict the trajectory. (*2) The coronavirus spread all over the world just as they warned. It can also converge and become an epidemic again.

I have suggested from early on that it is best to send out hospital ships and quarantine people there. Once the hospital is infected, the infection will spread widely. There are 35 ships in the U.S., and each ship can hold 1,000 patients. Japan is demanded to take such measures.

Read more:
One-of-a-Kind Coronavirus Was Artificially Produced? - The Liberty Web English

Our genes know kindness is the best medicine – Brainerd Dispatch

Editor's note: Life can be stressful, and many of us have a hard time administering self-care. The current world situation ripe with conflicts, shortages and a pandemic makes things even harder. Dr. Amit Sood, formerly of Mayo Clinic and now head of the Global Center for Resiliency and Wellbeing, is the author of books including "The Mayo Clinic Handbook for Happiness" and "SMART with Dr. Sood, and creator of the mobile app Zizo: Your Resilience Pal. Now, he is writing a weekly column answering readers' questions on these topics. See the tagline to learn how to send him your questions, and he will answer in future columns.

Dear friend,

Of the hundreds of ice-creams I have eaten so far, the only one I remember is the ice-cream I never ate.

That was in 1993. My wife Richa and I were sitting outside a shop in the sweltering New Delhi. We had just bought an ice cream to cool down. From the corner of my eye, I saw a little boy who could use a few calories. I walked up to him and offered my cone that he gladly took. I have savored the gleam I saw in his eyes at least a dozen times since then.

In a very interesting study, researchers looked at the genetic fingerprint of the two types of happiness hedonistic (self-centric) and eudaimonic (other-centric). People who were hedonistically happy had a higher inflammatory and lower anti-viral gene expression. It was just the opposite for the eudaimonic ones. With many illnesses caused by inflammation, you can see why this is so important for our health.

My take on this research is that our genes and the immune system know what is right for us and society. In the current times when a healthy immune system is extremely important for us, promoting kindness is imperative.

Kindness, research shows, pays three times over. Your kind words and actions enhance your health and wellbeing, help others, and the memory of kind actions by itself enhances your wellbeing. A very simple way to enhance your self-worth and happiness today is to count your previous kind actions.

I suggest take out a pen and paper and write the three most selfless things you have done in your life. If you feel up to it, share your experience with someone. Just counting previous acts of kindness can enhance your self-worth and bring happiness to others (you guessed it right witnessing or hearing about others kind actions also increases happiness).

In kindness,

Amit

Dr. Amit Sood answers your questions about stress, resilience, happiness, relationships, and related topics in his column. Email dearfriend@postbulletin.com.

Read the original post:
Our genes know kindness is the best medicine - Brainerd Dispatch

Innovation Wrap: Microscopic Robots, Asteroid Mining, A Flurry Of IPOs – ShareCafe

Heres your wrap of the latest technology, innovation, and finance news.

Robotics

UPenn researchers are building an army of microscopic robots. One day they could help us explore the world, or the human body, at a microscopic scale.

Through a process similar to that used in creating circuit boards, Miskin and his team were able to mass-produce more than a million of the microrobots, each of which is smaller than a tenth of a millimetre and is only visible under a microscope.

Spot has found a new job. Ford Motor Company is using two of the dog-like robots to map out their 200,000 square-metre Van Dyke Transmission Plant in Detroit. The data will be used to create a digital twin of the facility that will help Ford engineers better plan out process improvements, at a lower cost than traditional methods.

Over the years, factory plans get out of date as things are moved around and new equipment is brought in. Surveying the transmission plant by hand would take weeks and cost some $300,000. Ford reckons that Fluffy and Spot, which can both climb stairs and crawl into hard-to-reach areas, will cut the time required by half and complete the job for a fraction of the cost.

Biology

Harvard University researchers are helping mice keep weight off by using gene-editing to turn some of their regular white fat cells into energy-burning brown fat cells (see their paper).

In the future, this technique could potentially be used to treat people affected by obesity and metabolic disorders, says Tseng. It could be possible to remove a small amount of a persons white fat, engineer it into brown-like fat and re-implant it, she says.

Synthego, an AI-driven gene-editing startup founded by former SpaceX engineers, has raised $100 million.

Synthegos tools all of which are cloud-hosted cover over 120,000 genomes and 9,000 species. They provide guides to knock out genes with ostensibly minimal collateral effects. Underlying machine learning models predict overall editing efficiencies and even the set of mutations created for any given edit. Guide RNAs and cell engineering services for mammalian cell lines, primary cells, and more aid with editing experiments, along with guides that can be modified to resist degradation and prevent damaging immune responses.

Health

Stanford University researchers have found a way to wake dormant stem cells and grow new cartilage in the joints of arthritic mice (see their paper).

Primitive cells that can be transformed into new cartilage lie dormant at the ends of bones, the researchers reported in Nature Medicine. The cells just have to be awakened and stimulated to grow.

There is no cure for herpes, but were one step closer after researchers used gene therapy to significantly decrease latent infections in mice (see their paper).

This is the first time that anybody has been able to go in and actually eliminate most of herpes in a body, said Jerome, who is also spearheading research at Fred Hutch and the University of Washington on COVID-19. It is a completely different approach to herpes therapy than anybodys ever had before.

Gaming

CD Projekt announced a new mobile augmented reality game, The Witcher: Monster Slayer which is reminiscent of Pokmon Go. CD Projekts stock rose 7% on the day.

Are you familiar with Roblox? The Economist highlighted the game as one of the biggest entertainment success stories of the pandemic with more than 164 million active users and 2m+ creators.

Roblox is not itself a video game, but rather a game-creation platform. Users can design and build their own games and worlds using icons and pre-fabricated Lego-like blocks, rather than code, and then easily share them with friends.

Felipe Pepe concluded that Roblox is a MUD for the TikTok generation in a fascinating history of MUDs, virtual worlds, and MMORPGs. I spent a good deal of time playing MUDs growing up (and first learnt to program in one), so theyll always have a special place in my heart.

Renewables

The UK government has reduced its estimate of 2025 wind and solar costs by 30-50%.

The reasons for the renewable cost reductions are well documented. They include technological learning in the industry with larger, more efficient manufacturing plants for solar and larger turbines for wind but also operational experience, longer project lifetimes and cheaper finance.

French renewables developer Neoen is planning a $3 billion wind, solar, and storage project in South Australia.

The plan proposes a total of 1,200MW of wind energy, 600MW of solar PV, and 900MW/1800MWh of battery storage, an extremely large battery as Neoen describes it that will dwarf the 150MW/194MWh Tesla battery known officially as the Hornsdale Power Reserve.

Finance

Even great scientists like Sir Isaac Newton can get caught up in bubbles.

Newton had a simple explanation for his lapse. At the crucial moment, hed lost his mind. Or rather, others around him had lost theirs. I can calculate the motions of the heavenly bodies, his niece recalled him saying, but not the madness of the people.

It must be IPO season! Several companies filed for IPO (or a direct listing) fintech giant Ant Group, game engine developer Unity Software (S-1), data warehouse company Snowflake (S-1), data analytics company Palantir Technologies (S-1), work management tool Asana (S-1), business intelligence software company Sumo Logic (S-1), and developer tool company JFrog (S-1).

Other Snippets

DARPAs AlphaDogfight trials concluded with an AI pilot winning a flawless victory against a highly-trained US Air Force F-16 pilot.

Stratechery wrote a good summary of why Australias News Media Bargaining Code makes no sense.

Google released the alpha version of Jetpack Compose, which promises to let Android developers write apps with dramatically less code.

K-pop continues to break YouTube viewing records with BTSs new music video for Dynamite racking up 98 million views within 24 hours. This surpassed previous record Blackpink which saw 86 million views within 24 hours for How You Like That back in June.

Kurzgesagt explained the basics of asteroid mining.^

^ Well, kind of As Troy McCann, founder of space startup accelerator Moonshot, correctly points out, asteroid mining will focus on the use of the materials in space, not on earth, given materials in space are always more valuable than those on earth as they embed the cost to get the material there. As such, this video doesnt really represent early asteroid mining efforts which are more likely to focus on water in space rather than delivering material to earth.

Visit link:
Innovation Wrap: Microscopic Robots, Asteroid Mining, A Flurry Of IPOs - ShareCafe

Study reveals genetic mutations may be linked to infertility, early menopause – Devdiscourse

A new study identifies a specific gene's previously unknown role in fertility. Analysing genetic data in people, the researchers found an association between mutations in this gene and early menopause. The study appears in the journal of Science Advances.

The human gene -- called nuclear envelope membrane protein 1 (NEMP1) -- is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

"We blocked some gene expression in fruit flies but found that their eyes were fine," said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. "So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs." Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the egg's nucleus -- the vital compartment that holds half of an organism's chromosomes -- looked like a floppy balloon.

"This gene is expressed throughout the body, but we didn't see this floppy balloon structure in the nuclei of any other cells," said McNeill, also a professor of developmental biology. "That was a hint we'd stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. It's so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. It's not a huge leap to suspect it has a role in people as well." To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus's membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleus's membrane was much softer.

"It's interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people," McNeill said. "We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that they're born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause." McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovary's stressful environment. With age, ovaries develop strands of collagen with the potential to create mechanical stress not present in embryonic ovaries.

"If you have a softer nucleus, maybe it can't handle that environment," McNeill said. "This could be the cue that triggers the death of eggs. We don't know yet, but we're planning studies to address this question." Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anaemic, meaning they lacked red blood cells.

"Normal adult red blood cells lack a nucleus," McNeill said. "There's a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice aren't doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation." The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

"We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope," McNeill said. "It's possible there are perfectly healthy women walking around who lack the NEMP protein. If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations -- restore NEMP, for example, or find some other way to support nuclear envelope stiffness." (ANI)

See the original post here:
Study reveals genetic mutations may be linked to infertility, early menopause - Devdiscourse

Case Western Reserve University-led team develops new approach to treat certain neurological diseases – Mirage News

A team led by Case Western Reserve University medical researchers has developed a potential treatment method for Pelizaeus-Merzbacher disease (PMD), a fatal neurological disorder that produces severe movement, motor and cognitive dysfunction in children. It results from genetic mutations that prevent the body from properly making myelin, the protective insulation around nerve cells.

Paul Tesar, professor of genetics and genome sciences, School of Medicine

Using mouse models, the researchers identified and validated a new treatment target-a toxic protein resulting from the genetic mutation. Next, they successfully used a family of drugs known as ASOs (antisense oligonucleotides) to target the ribonucleic acid (RNA) strands that created the abnormal protein to stop its production. This treatment reduced PMDs hallmark symptoms and extended lifespan, establishing the clinical potential of this approach.

By demonstrating effective delivery of the ASOs to myelin-producing cells in the nervous system, researchers raised the prospect for using this method to treat other myelin disorders that result from dysfunction within these cells, including multiple sclerosis (MS).

Their research was published online July 1 in the journal Nature.

The pre-clinical results were profound. PMD mouse models that typically die within a few weeks of birth were able to live a full lifespan after treatment, said Paul Tesar, principal investigator on the research, a professor in the Department of Genetics and Genome Sciences at the School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics. Our results open the door for the development of the first treatment for PMD as well as a new therapeutic approach for other myelin disorders.

Study co-authors include an interdisciplinary team of researchers from the medical school, Ionis Pharmaceuticals Inc., a Carlsbad, California-based pioneer developer of RNA-targeted therapies, and Cleveland Clinic. First author Matthew Elitt worked in Tesars lab as a Case Western Reserve medical and graduate student.

PMD is a rare, genetic condition involving the brain and spinal cord that primarily affects boys. Symptoms can appear in early infancy and begin with jerky eye movements and abnormal head movements. Over time, children develop severe muscle weakness and stiffness, cognitive dysfunction, difficulty walking and fail to reach developmental milestones such as speaking. The disease cuts short life-expectancy, and people with the most severe cases die in childhood.

The disease results from errors in a gene called proteolipid protein 1 (PLP1). Normally, this gene produces proteolipid protein (PLP) a major component of myelin, which wraps and insulates nerve fibers to allow proper transmission of electrical signals in the nervous system. But a faulty PLP1 gene produces toxic proteins that kill myelin producing cells and prevent myelin from developing and functioning properly-resulting in the severe neurological dysfunction in PMD patients.

PMD impacts a few thousand people around the world. So far, no therapy has lessened symptoms or extended lifespans.

For nearly a decade, Tesar and his team have worked to better understand and develop new therapies for myelin disorders. They have had a series of successes, and their myelin-regenerating drugs for MS are now in commercial development.

In the current laboratory work, the researchers found that suppressing mutant PLP1 and its toxic protein restored myelin-producing cells, produced functioning myelin, reduced disease symptoms and extended lifespans.

After validating that PLP1 was their therapeutic target, the researchers pursued pre-clinical treatment options. They knew mutations in the PLP1 gene produced faulty RNA strands that, in turn, created the toxic PLP protein.

Additional team members included Lilianne Barbar, Elizabeth Shick, Yuka Maeno-Hikichi, Mayur Madhavan, Kevin Allan, Baraa Nawash, Artur Gevorgyan, Stevephen Hung, Zachary Nevin, Hannah Olsen, Daniela Schlatzer, David LePage, Weihong Jiang and Ronald Conlon from Case Western Reserve University School of Medicine; Berit Powers, Hien Zhao, Adam Swayze and Frank Rigo from Ionis Pharmaceuticals; and Midori Hitomi from Cleveland Clinic.

This research was supported by grants from the National Institutes of Health, New York Stem Cell Foundation and European Leukodystrophy Association. Philanthropic support was provided by the Geller, Goodman, Fakhouri, Long, Matreyak, Peterson and Weidenthal families and the CWRU Research Institute for Childrens Health.

See original here:
Case Western Reserve University-led team develops new approach to treat certain neurological diseases - Mirage News

Governor Cooper Announces Genetic Medicine Company Will Create 201 Jobs in Durham County – NC Dept of Commerce

Governor Roy Cooper announced today that Beam Therapeutics (Nasdaq; BEAM), a biotechnology company developing precision medicines through DNA base editing, plans to build a manufacturing facility in North Carolinas Research Triangle Park, creating 201 jobs. Over a period of 5 years, the company expects to invest $83 million in the facility, which will support clinical and commercial manufacturing for the companys novel base editing programs.

"North Carolina is a leader in biotechnology, from the research in our labs to the states biomanufacturers, said Governor Cooper. Companies like Beam Therapeutics work in developing precision medicines will help keep North Carolina on the cutting edge of this industry.

Beam Therapeutics, with headquarters in Cambridge, Massachusetts, develops precision genetic medicines through base editing. The foundational level of genetic information is a single base letter in DNA, and an error to a single letter, known as a point mutation, can cause disease. Base editors have the ability to rewrite just a single letter, and thereby intervene at the most foundational level. Beams proprietary base editors create precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This enables a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs.

We believe investment in strategic manufacturing capabilities is an important component of fully realizing the power of our base editing technology and achieving our vision to provide life-long cures to patients suffering from serious diseases, said John Evans, CEO of Beam Therapeutics. Research Triangle Park is a thriving biopharmaceutical hub, providing significant access to the broad range of talent we will need to make this vision a reality.

Although wages will vary depending on position, the average salary for the new positions will be $102,654. The average wage in Durham County is $71,756. The state and local area will see a yearly economic impact of more than $20.6 million from this companys new payroll.

"North Carolina has been a world leader in biotechnology for many years, but were not resting on our past accomplishments, said North Carolina Commerce Secretary Anthony M. Copeland. Beam Therapeutics joins a host of gene therapy companies that are keeping North Carolina at the forefront of this new frontier of medicine.

Beam Therapeutics project in North Carolina will be facilitated, in part, by a Job Development Investment Grant (JDIG) approved by the states Economic Investment Committee earlier today. Over the course of 12 years, the project is estimated to grow the states economy by $1.36 billion. Using a formula that takes into account the new tax revenues generated by the new jobs, the agreement authorizes the potential reimbursement to the company of up to $3,237,750, spread over 12 years. Payments for all JDIGs only occur following performance verification by the departments of Commerce and Revenue that the company has met its incremental job creation and investment targets. JDIG projects result in positive net tax revenue to the state treasury, even after taking into consideration the grants reimbursement payments to a given company.

Because Beam Therapeutics chose a site in Durham County, classified by the states economic tier system as Tier 3, the companys JDIG agreement also calls for moving as much as $1,079,250 into the states Industrial Development Fund Utility Account. The Utility Account helps rural communities finance necessary infrastructure upgrades to attract future business. Even when new jobs are created in a Tier 3 county such as Durham, the new tax revenue generated through JDIG grants helps more economically challenged communities elsewhere in the state. More information on the states economic tier designations is available here.

In addition to the North Carolina Department of Commerce and the Economic Development Partnership of N.C., other key partners on this project were the the North Carolina Community College System, the North Carolina Biotechnology Center, Durham County, and the Greater Durham Chamber of Commerce.

View original post here:
Governor Cooper Announces Genetic Medicine Company Will Create 201 Jobs in Durham County - NC Dept of Commerce

BEAM THERAPEUTICS : Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) – marketscreener.com

The following discussion and analysis of our financial condition and results ofoperations should be read in conjunction with our condensed consolidatedfinancial statements and the related notes to those statements includedelsewhere in this Quarterly Report on Form 10-Q. In addition to historicalfinancial information, the following discussion and analysis containsforward-looking statements that involve risks, uncertainties and assumptions.Some of the numbers included herein have been rounded for the convenience ofpresentation. Our actual results may differ materially from those anticipated inthese forward-looking statements as a result of many factors, including thosediscussed in "Risk Factors" in Part II, Item 1A. and elsewhere in this QuarterlyReport on Form 10-Q.

Overview

We are a biotechnology company committed to creating a new class of precisiongenetic medicines based on our proprietary base editing technology, with avision of providing life-long cures to patients suffering from serious diseases.Our proprietary base editing technology potentially enables an entirely newclass of precision genetic medicines that targets a single base in the genomewithout making a double-stranded break in the DNA. This approach uses a chemicalreaction designed to create precise, predictable and efficient genetic outcomesat the targeted sequence. Our novel base editors have two principal components:(i) a CRISPR protein, bound to a guide RNA, that leverages the establishedDNA-targeting ability of CRISPR, but modified to not cause a double-strandedbreak, and (ii) a base editing enzyme, such as a deaminase, which carries outthe desired chemical modification of the target DNA base. We believe this designcontributes to a more precise and efficient edit compared to traditional geneediting methods. The precision of our editors has the potential to increase theimpact of gene editing for a broad range of therapeutic applications. Bybuilding on the significant recent advances in the field of genetic medicine, webelieve we will be able to rapidly advance our portfolio of novel base editingprograms.

Existing gene editing technologies operate by creating targeted double-strandedbreaks in the DNA, and then rely on cellular mechanisms to complete the editingprocess. Such approaches can be effective in the disruption of gene expression;however, they are inefficient for precise repair or alteration of genesequences, and can result in unwanted DNA modifications. We believe our baseediting platform offers meaningful advantages over existing approaches in geneediting and gene therapy, including:

We are currently advancing a broad, diversified portfolio of base editingprograms against distinct editing targets. To unlock the full potential of ourbase editing technology across a wide range of therapeutic applications, we arepursuing a comprehensive suite of clinically validated delivery modalities inparallel. For a given tissue type, we use the delivery modality with the mostcompelling biodistribution. Our programs are organized by delivery modality intothree distinct pipelines: electroporation for efficient delivery to blood cellsand immune cells ex vivo; lipid nanoparticles, or LNPs, for non-viral in vivodelivery to the liver and potentially other organs in the future; andadeno-associated viral vectors, or AAV, for viral delivery to the eye andcentral nervous system, or CNS.

Our base editing portfolio

The elegance and simplicity of the base editing approach provides for anefficient, precise, and highly versatile gene editing system, capable of genecorrection, gene silencing/gene activation, and multiplex editing of severalgenes simultaneously. We believe the flexibility and versatility of our baseeditors may lead to broad therapeutic applicability and transformationalpotential for the field of precision genetic medicines.

We have achieved proof-of-concept in vivo with long-term engraftment of ex vivobase edited human CD34 cells in mice for BEAM-101, our program that reproducessingle base changes seen in individuals with Hereditary Persistence of FetalHemoglobin, or HPFH, that protects them from the effects of mutations causingsickle cell disease or thalassemia. Additionally, in the second quarter of 2020,

--------------------------------------------------------------------------------

we published data on BEAM-102, our program to directly correct the causativemutation in sickle cell disease by recreating a naturally-occurring humanhemoglobin variant, Hb-G Makassar. The Makassar variant does not causehemoglobin to polymerize, or red cells to sickle and, therefore, edited cellsare cured through elimination of the disease-causing protein. With respect toour liver disease programs, also in the second quarter of 2020, we have shownthe ability to directly correct the mutation causing alpha-1 antitrypsindeficiency, providing both in vitro and in vivo proof of concept for baseediting to correct this disease. We have also successfully demonstratedfeasibility of base editing with each of our three delivery modalities inrelevant cell types for electroporation and AAV and in vivo in mice for LNP.

Beyond the in vivo proofs-of-concept already established, we expect to achieveadditional milestones in 2020, including the publication of additional in vivobase editing data and, provided the COVID-19 pandemic does not cause ourtimelines to slip materially, initiation of investigational new drug, or IND,enabling studies for at least one of our lead programs. We expect to submit aninitial wave of IND filings from this portfolio, and we remain on track to fileour first IND in 2021.

The modularity of our platform means that establishing preclinicalproof-of-concept of base editing using a particular delivery modality will alsopotentially reduce risk and accelerate the timeline for additional productcandidates that we may develop targeting the same tissue. In some cases, a newproduct candidate may only require changing the guide RNA. Subsequent programsusing the same delivery modality can also take advantage of shared capabilitiesand resources of earlier programs. In this way, we view each delivery modalityas its own unique pipeline, where the success of any one program may pave theway for a large number of additional programs to progress quickly to the clinic.

Ex vivo electroporation for hematologic diseases and oncology

Sickle Cell Disease and Beta-Thalassemia

Sickle cell disease, a severe inherited blood disease, is caused by a singlepoint mutation, E6V, in the beta globin gene at the sixth amino acid. Thismutation causes the mutated form of hemoglobin, or HbS, to aggregate into long,rigid molecules that bend red blood cells into a sickle shape under conditionsof low oxygen. Sickled cells obstruct blood vessels and die prematurely,ultimately resulting in anemia, severe pain (crises), infections, stroke, organfailure, and early death. Sickle cell disease is the most common inherited blooddisorder in the United States, affecting an estimated 100,000 individuals, ofwhich a significant proportion are of African-American descent (1:365 births).Beta-thalassemia is another inherited blood disorder characterized by severeanemia caused by reduced production of functional hemoglobin due to insufficientexpression of the beta globin protein. Transfusion-dependent beta-thalassemia,or TDBT, is the most severe form of this disease, often requiring multipletransfusions per year. Patients with TDBT suffer from failure to thrive,persistent infections, and life-threatening anemia. The incidence of symptomaticbeta-thalassemia is estimated to be 1:100,000 worldwide, including 1:10,000 inEurope. In the United States, based on affected birth incidence of 0.7 in100,000 births, and increasing survival rates, we expect the population ofindividuals affected by this disease to be more than 1,400 and rising. The onlypotentially curative therapy currently available for patients with sickle celldisease or beta-thalassemia is allogeneic Hematopoietic Stem Cell Transplant, orHSCT; however, this procedure holds a high level of risk, particularlyGraft-versus-Host Disease, or GvHD, resulting in a low number of patients optingfor this treatment.

--------------------------------------------------------------------------------

We are using base editing to pursue two complementary approaches to treatingsickle cell disease and one to treat beta-thalassemia:

BEAM-101: Recreating naturally-occurring protective mutations to activate fetalhemoglobin

The beneficial effects of the fetal form of hemoglobin, or HbF, to compensatefor mutations in adult hemoglobin were first identified in individuals with acondition known as HPFH. Individuals who carry mutations that would havetypically caused them to be beta-thalassemia or sickle cell disease patients,but who also have HPFH, are asymptomatic or experience a much milder form oftheir disease. HPFH is caused by single base changes in the regulatory region ofthe genes, HBG1 and HBG2, which prevents binding of one or more repressorproteins and increases the expression of gamma globin, which forms part of theHbF tetramer.

Using base editing, we reproduce these specific, naturally occurring basechanges in the regulatory elements of the gamma globin genes, preventing bindingof repressor proteins and leading to re-activation of gamma globin expression,and thus the increase in gamma globin levels. Our in vitro and in vivocharacterization of BEAM-101 using ex vivo delivery achieved precise andefficient editing of human CD34+ hematopoietic stem and progenitor cells, orHSPCs, resulting in long-term engraftment and therapeutically-relevant increasesin target gene expression in mice.

In vitro characterization of BEAM-101:

In vivo performance of BEAM-101:

BEAM-102: Direct correction of the sickle cell mutation

Our second base editing approach for sickle cell disease, BEAM-102, is a directcorrection of the causative sickle mutation at position 6 of the beta globingene. By making a single A-to-G edit, we have demonstrated in primary humanCD34+ cells isolated from sickle cell disease patients the ability to create thenaturally occurring Makassar variant of hemoglobin. This variant, which wasoriginally identified in humans in 1970, has the same function as the wild-typevariant and does not cause sickle cell disease. Distinct from other approaches,cells that are successfully edited in this way are fully corrected, no longercontaining the sickle protein.

BEAM-102 uses ex vivo delivery of our adenine base editor, or ABE, to edit CD34+HSPCs. In cells isolated from donors with sickle cell disease, we achievedgreater than 80% correction of the sickle point mutation to the HbG-Makassarvariant, following in vitro erythroid differentiation. As expected, we observedthe simultaneous reduction of HbS to less than 20% of control levels. More than70% of erythroid colonies derived from edited patient cells showed biallelicediting (yielding cells that no longer produce any sickle protein at all), 20%had monoallelic editing (with one sickle allele and one corrected allele, likelyconferring a level of protection similar to patients with "sickle cell trait"who do not show significant symptoms of disease), and 2% were unedited. Further,the correction of the HbS protein to the HbG-Makassar variant was shown tosignificantly reduce the propensity of in vitro differentiated erythroid cellsto sickle when subjected to hypoxia. These findings represent therapeutic levelsof correction and support advancement of this program to potentially address theunderlying genetic cause of sickle cell disease. Published modeling studiessuggest that as little as 20% correction of HbS may be sufficient to cure thedisease.

Ex vivo electroporation for multiplex editing of advanced cell therapies

CAR-T Cell Therapies in Immunology/Oncology

We believe base editing is an ideal tool to simultaneously multiplex edit manygenes without unintended on-target effects, such as genomic rearrangements oractivation of the p53 pathway, that can result from simultaneous editing withnucleases through the creation of double strand breaks. The ability to create alarge number of multiplex edits in T cells could endow CAR-T cells and other

--------------------------------------------------------------------------------

cell therapies with combinations of features that may dramatically enhance theirtherapeutic potential in treating hematological or solid tumors.

Proof-of-concept experiments have now demonstrated the ability of base editorsto efficiently modify up to 8 genomic loci simultaneously in primary human Tcells with efficiencies ranging from 85-95% as measured by flow cytometry oftarget protein knockdown. Importantly, these results are achieved without thegeneration of chromosomal rearrangements, as detected by a sensitive method(UDiTaSTM) and with no loss of cell viability from editing. The proof-of-conceptexperiments have also demonstrated robust T cell killing of target tumor cells.

Our initial focus will be on hematologic malignancies, and we are developingallogeneic CAR-T product candidates that have four edits each. This multiplexediting will enable a high degree of engineering and functionality, includingthe following simultaneous edits:

The initial indications that we plan to target with these product candidates arerelapsed, refractory, pediatric T-cell Acute Lymphoblastic Leukemia, or T-ALL,and pediatric Acute Myeloid Leukemia, or AML. We believe that our approach hasthe potential to produce higher response rates and deeper remissions thanexisting approaches.

Non-Viral delivery for liver diseases

Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency, or Alpha-1, is a severe inherited geneticdisorder that can cause progressive lung and liver disease. The most severe formof ALPHA-1 arises when a patient has a point mutation in both copies of theSERPINA1 gene at amino acid 342 position (E342K, also known as the PiZ mutationor the "Z" allele). This point mutation causes alpha-1 antitrypsin, or AAT, tomisfold, accumulating inside liver cells rather than being secreted, resultingin very low levels (10%-15%) of circulating AAT. As a consequence, the lung isleft unprotected from neutrophil elastase, resulting in progressive, destructivechanges in the lung, such as emphysema, which can result in the need for lungtransplants. The mutant AAT protein also accumulates in the liver, causing liverinflammation and cirrhosis, which can ultimately cause liver failure or cancerand require patients to undergo a liver transplant. It is estimated thatapproximately 60,000 individuals in the United States have two copies of the Zallele. There are currently no curative treatments for patients with ALPHA-1.

With the high efficiency and precision of our base editors, we aim to utilizeour ABEs to enable the programmable conversion of A-to-T and G-to-C base pairsand precisely correct the E342K point mutation back to the wild type sequence.

For a recent study, we engineered novel ABEs and guide RNAs capable ofcorrecting the PiZ mutation, and then applied a proprietary non-viral lipidnanoparticle formulation to deliver the optimized reagents to the livers of aPiZ transgenic mouse model. This direct editing approach resulted in an averageof 16.9% correction of beneficial alleles at 7 days and 28.8% at three months.This significant increase over the period suggests that corrected hepatocytesmay have a proliferative advantage relative to uncorrected cells. In addition,treated mice demonstrate decreased alpha-1 antitrypsin, or A1AT, globule burdenwithin the liver and a durable, significant increase in serum A1AT activeprotein at three months, roughly 4.9-fold higher than in controls, levels whichwe believe would be therapeutic if achieved in patients. These data indicate thepotential for base editing as a one-time therapy to treat both lung and livermanifestations of Alpha-1 antitrypsin deficiency.

Glycogen Storage Disease 1a

Glycogen Storage Disease Type 1A, also known as Von Gierke disease, is an inborndisorder of glucose metabolism caused by mutations in the G6PC gene, whichresults in low blood glucose levels that can be fatal if patients do not adhereto a strict regimen of slow-release forms of glucose, administered every one tofour hours (including overnight). There are no disease-modifying therapiesavailable for patients with GSD1a.

Our approach to treating patients with glycogen storage disease 1a, or GSD1a, isto apply base editing via LNP delivery to repair the two most prevalentmutations that cause the disease, R83C and Q347X. It is estimated that thesetwo-point mutations account for 900 and 500 patients, respectively, in theUnited States, representing approximately 59% of all GSD1a patients. Animalstudies have shown that as little as 11% of normal G6Pase activity in livercells is sufficient to restore fasting glucose; however, this level must bemaintained in order to preserve glucose control and alleviate other serious, andpotentially fatal, GSD1a sequelae

--------------------------------------------------------------------------------

We have identified product candidates that can correct up to 80% of the allelesin cells harboring the Q347X point mutation and approximately 60% of the allelesin cells harboring the R83C mutation as shown in the figures below. Correctionof at least 11% is expected to be clinically relevant and potentially diseasemodifying for GSD1a patients.

Viral delivery for ocular and CNS disorders

Stargardt Disease

Stargardt Disease is an inherited disorder of the central region of the retina,causing progressive vision loss typically beginning in adolescence andultimately leading to central and night vision blindness. The most prevalentmutation in the ABCA4 gene that leads to Stargardt disease is the G1961E pointmutation. Approximately 5,500 individuals in the United States are affected bythis mutation. Our base editing approach is to repair the G1961E point mutationin the ABCA4 gene. Disease modeling using tiny spot stimuli, or light stimulithrough holes that are equivalent in size to a single photoreceptor cell,suggests that only 12%-20% of these cells are sufficient to preserve vision. Weanticipate, therefore, that editing percentages in the range of 12%-20% of thesecells would be disease-modifying, since each edited cell will be fully correctedand protected from the biochemical defect.

Given that the base editor is larger than the packaging capacity of a singleAAV, we use a split AAV system that delivers the base editor via two AAVvectors. Once inside the cell, the two halves of the editor are recombined tocreate a functional base editor. In a human retinal pigment epithelial cell line(ARPE-19 cells) in which we have knocked in the ABCA4 G1961E point mutation, wehave demonstrated the precise correction of approximately 75% of the diseasealleles at 5 weeks after dual infection with the split AAV system.

Collaborations

We believe our base editing technology has potential across a broad array ofgenetic diseases. To fully realize this potential, we have established and willcontinue to seek out innovative collaborations, licenses, and strategicalliances with pioneering companies and with leading academic and researchinstitutions. Additionally, we have and will continue to pursue relationshipsthat potentially allow us to accelerate our preclinical research and developmentefforts. These relationships will allow us to uphold our vision of maximizingthe potential of base editing to provide life-long cures for patients sufferingfrom serious diseases.

Ex vivo electroporation for hematologic diseases and oncology

Boston Children's Hospital

In July 2020, we formed a strategic alliance with Boston Children's Hospital.Under the terms of the agreement, we will sponsor research programs at BostonChildren's to facilitate development of disease-specific therapies using ourproprietary base editing technology. Boston Children's will also serve as aclinical site to advance bench-to-bedside translation of our pipeline acrosscertain therapeutic areas of interest, including programs in sickle cell diseaseand pediatric leukemias and exploration of new programs targeting otherdiseases.

Magenta Therapeutics

In June 2020, we announced a non-exclusive research and clinical collaborationagreement with Magenta Therapeutics to evaluate the potential utility ofMGTA-117, Magenta's novel targeted ADC for conditioning of patients with sicklecell disease and beta-thalassemia receiving our base editing therapies.Conditioning is a critical component necessary to prepare a patient's body toreceive the edited cells, which carry the corrected gene and must engraft in thepatient's bone marrow in order to be effective. Today's conditioning regimensrely on nonspecific chemotherapy or radiation, which are associated withsignificant toxicities. MGTA-117 precisely targets only hematopoietic stem andprogenitor cells, sparing immune cells, and has shown high selectivity, potentefficacy, wide safety margins and broad tolerability in non-human primatemodels. MGTA-117 may be capable of clearing space in bone marrow to supportlong-term engraftment and rapid recovery in patients. Combining the precision ofour base editing technology with the more targeted conditioning regimen enabledby MGTA-117 could further improve therapeutic outcomes for patients sufferingfrom these severe diseases. We will be responsible for clinical trial costsrelated to development of our base editors when combined with MGTA-117, whileMagenta will continue to be responsible for all other development costs ofMGTA-117.

Non-Viral delivery for liver diseases

Verve Therapeutics

In April 2019, we entered into a collaboration and license agreement with Verve,a company focused on developing genetic medicines to safely edit the genome ofadults to permanently lower LDL cholesterol and triglyceride levels and therebytreat coronary heart disease. This collaboration allows us to fully realize thepotential of base editing in treating cardiovascular diseases, an area outsideof our core focus where the Verve team has significant, world-class expertise.Under the terms of the agreement, Verve received exclusive access to our baseediting technology, gene editing, and delivery technologies for humantherapeutic applications against certain cardiovascular targets. In exchange, wereceived 2,556,322 shares of Verve common stock. Additionally, we will receivemilestone payments for certain clinical and regulatory events and retains theoption, after the completion of Phase 1 studies, to participate in futuredevelopment and commercialization, and share 50 percent of U.S. profits andlosses, for any product directed

--------------------------------------------------------------------------------

against these targets. Verve granted to us a non-exclusive license underknow-how and patents controlled by Verve, and an interest in joint collaborationtechnology. Either party may owe the other party other milestone payments forcertain clinical and regulatory events related to the delivery technologyproducts. Royalty payments may become due by either party to the other based onthe net sales of any commercialized delivery technology products under theagreement.

In June 2020, Verve reported preclinical proof-of-concept data in non-humanprimates that demonstrated the successful use of adenine base editors to turnoff a gene in the liver. Utilizing ABE technology licensed from us and anoptimized guide RNA packaged in an engineered lipid nanoparticle, Verveevaluated in vivo liver base editing to turn off proprotein convertasesubtilisin/kexin type 9 (PCSK9), a gene whose protein product elevates blood LDLcholesterol or angiopoietin-like protein 3 (ANGPTL3), a gene whose proteinproduct elevates blood triglyceride-rich lipoproteins. We believe theseproof-of-concept data, which show we can safely edit the primate genome,represent the first successful application of the base editing technology innon-human primates

In two separate studies, seven animals were treated with the drug producttargeting the PCSK9 gene and seven additional animals with the drug producttargeting the ANGPTL3 gene. Whole liver editing, blood protein and lipid levelswere measured at two weeks and compared to baseline. The program targeting PCSK9showed an average of 67% whole liver PCSK9 editing, which translated into an 89%reduction in plasma PCSK9 protein and resulted in a 59% reduction in blood LDLcholesterol levels. The program targeting ANGPTL3 showed an average of 60% wholeliver ANGPTL3 editing, which translated into a 95% reduction in plasma ANGPTL3protein and resulted in a 64% reduction in blood triglyceride levels and 19%reduction in LDL cholesterol levels. In addition, in studies in primary humanhepatocytes, clear evidence of on-target editing was observed with no evidenceof off-target editing.

Per the terms of our agreement with Verve, we can exercise our right toparticipate in the future development and commercialization of any programs atthe completion of Phase I studies.

Viral delivery for ophthalmology and CNS diseases

IOB

In July 2020, we announced a research collaboration with the Institute ofMolecular and Clinical Ophthalmology Basel (IOB). Founded in 2018 by aconsortium that includes Novartis, the University Hospital of Basel and theUniversity of Basel, IOB is a leader in basic and translational research aimedat treating impaired vision and blindness. Clinical scientists at IOB have alsohelped to develop better ways to measure how vision is impacted by Stargardtdisease. Additionally, researchers at IOB have developed living models of theretina, known as organoids, which can be used to test novel therapies. Under theterms of the agreement, the companies will leverage IOB's unique expertise inthe field of ophthalmology along with our novel base editing technology toadvance programs directed to the treatment of certain ocular diseases, includingStargardt disease.

Manufacturing

To realize the full potential of base editors as a new class of medicines, weare building customized and integrated capabilities across discovery,manufacturing, and preclinical and clinical development. Due to the criticalimportance of high-quality manufacturing and control of production timing andknow-how, we have taken steps toward establishing our own manufacturingfacility, which will provide us the flexibility to manufacture numerousdifferent drug product modalities. We believe this investment will maximize thevalue of our portfolio and capabilities, the probability of technical success ofour programs, and the speed at which we can provide life-long cures to patients.

In August 2020, we entered into a lease agreement with Alexandria Real EstateEquities, Inc. to build a 100,000 square foot current Good ManufacturingPractice, or cGMP, compliant manufacturing facility in Research Triangle Park,North Carolina intended to support a broad range of clinical programs. We willinvest up to $83 million over a five-year period and anticipate that thefacility will be operational by the first quarter of 2023. The project will befacilitated, in part, by a JDIG approved by the North Carolina EconomicInvestment Committee, which authorizes potential reimbursements based on new taxrevenues generated through the project. The facility will be designed to supportmanufacturing for our ex vivo cell therapy programs in hematology and oncologyand in vivo non-viral delivery programs for liver diseases, with flexibility tosupport manufacturing of our viral delivery programs, and ultimately, scale-upto support potential commercial supply.

For our initial waves of clinical programs, we will use contract manufacturingorganizations, or CMOs, with relevant manufacturing experience in geneticmedicines.

COVID-19

With the ongoing concern related to the COVID-19 pandemic, we have maintainedand expanded the business continuity plans, implemented in the first six monthsof 2020, to address and mitigate the impact of the COVID-19 pandemic on ourbusiness. In March 2020, to protect the health of our employees, and theirfamilies and communities, we restricted access to our offices to personnel whoperformed critical activities that must be completed on-site, limited the numberof such personnel that can be present at our facilities at any one time, andrequested that most of our employees work remotely. In May 2020, as certainstates eased restrictions, we established new protocols to better allow our fulllaboratory staff access to our facilities. These protocols included severalshifts

--------------------------------------------------------------------------------

working over a seven days week protocol. We expect to continue incurringadditional costs to ensure we adhere to the guidelines instituted by the Centersfor Disease Control and to provide a safe working environment to our onsiteemployees.

The extent to which the COVID-19 pandemic impacts our business, our corporatedevelopment objectives, results of operations and financial condition, includingand the value of and market for our common stock, will depend on futuredevelopments that are highly uncertain and cannot be predicted with confidenceat this time, such as the ultimate duration of the pandemic, travelrestrictions, quarantines, social distancing and business closure requirements,and the effectiveness of actions taken globally to contain and treat thedisease. Disruptions to the global economy, disruption of global healthcaresystems, and other significant impacts of the COVID-19 pandemic could have amaterial adverse effect on our business, financial condition, results ofoperations and growth prospects.

While the COVID-19 pandemic did not significantly impact our business or resultsof operations during the six months ended June 30, 2020, the length and extentof the pandemic, its consequences, and containment efforts will determine thefuture impact on our operations and financial condition.

Critical accounting policies and significant judgements

Our critical accounting policies are those policies which require the mostsignificant judgments and estimates in the preparation of our condensedconsolidated financial statements. We have determined that our most criticalaccounting policies are those relating to stock-based compensation, variableinterest entities, fair value measurements, and leases. There have been nosignificant changes to our existing critical accounting policies discussed inour Annual Report on Form 10-K for the year ended December 31, 2019.

Financial operations overview

General

We were incorporated on January 25, 2017 and commenced operations shortlythereafter. Since our inception, we have devoted substantially all of ourresources to building our base editing platform and advancing development of ourportfolio of programs, establishing and protecting our intellectual property,conducting research and development activities, organizing and staffing ourcompany, business planning, raising capital and providing general andadministrative support for these operations. To date, we have financed ouroperations primarily through the sales of our redeemable convertible preferredstock and proceeds from our IPO.

We are a development stage company, and all of our programs are at a preclinicalstage of development. To date, we have not generated any revenue from productsales and do not expect to generate revenue from the sale of products for theforeseeable future. Since inception we have incurred significant operatinglosses. Our net losses for the six months ended June 30, 2020 and 2019 were$64.7 million and $31.5 million, respectively. As of June 30, 2020, we had anaccumulated deficit of $267.7 million. We expect to continue to incursignificant expenses and increasing operating losses in connection with ongoingdevelopment activities related to our portfolio of programs as we continue ourpreclinical development of product candidates; advance these product candidatestoward clinical development; further develop our base editing platform; researchactivities as we seek to discover and develop additional product candidates;maintenance, expansion enforcement, defense, and protection of our intellectualproperty portfolio; and hiring research and development, clinical and commercialpersonnel. In addition, we expect to continue to incur additional costsassociated with operating as a public company.

As a result of these anticipated expenditures, we will need additional financingto support our continuing operations and pursue our growth strategy. Until suchtime as we can generate significant revenue from product sales, if ever, weexpect to finance our operations through a combination of equity offerings, debtfinancings, collaborations, strategic alliances, and licensing arrangements. Wemay be unable to raise additional funds or enter into such other agreements whenneeded on favorable terms or at all. Our inability to raise capital as and whenneeded would have a negative impact on our financial condition and our abilityto pursue our business strategy. We can give no assurance that we will be ableto secure such additional sources of funds to support our operations, or, ifsuch funds are available to us, that such additional funding will be sufficientto meet our needs.

Research and development expenses

Research and development expenses consist of costs incurred in performingresearch and development activities, which include:

--------------------------------------------------------------------------------

We expense research and development costs as incurred. Advance payments that wemake for goods or services to be received in the future for use in research anddevelopment activities are recorded as prepaid expenses. The prepaid amounts areexpensed as the benefits are consumed.

In the early phases of development, our research and development costs are oftendevoted to product platform and proof-of-concept studies that are notnecessarily allocable to a specific target, therefore, we have not yet beguntracking our expenses on a program-by-program basis.

We expect that our research and development expenses will increase substantiallyin connection with our planned preclinical and future clinical developmentactivities.

General and administrative expenses

General and administrative expenses consist primarily of salaries and otherrelated costs, including stock-based compensation, for personnel in ourexecutive, intellectual property, business development, finance, andadministrative functions. General and administrative expenses also include legalfees relating to intellectual property and corporate matters, professional feesfor accounting, auditing, tax and consulting services, insurance costs, travel,and direct and allocated facility related expenses and other operating costs.

We anticipate that our general and administrative expenses will increase in thefuture to support increased research and development activities. We also expectto incur increased costs associated with being a public company, including costsof accounting, audit, legal, regulatory and tax-related services associated withmaintaining compliance with Nasdaq and SEC requirements, director and officerinsurance costs, and investor and public relations costs.

Results of operations

Comparison of the three months ended June 30, 2020 and 2019

The following table summarizes our results of operations, together with thechange in dollars (in thousands):

License revenue was $6 thousand for the three months ended June 30, 2020 and2019 representing Verve license revenue recorded under the Collaboration andLicense Agreement executed in April 2019.

Research and development expenses

Research and development expenses were $19.4 million and $12.7 million for thethree months ended June 30, 2020 and 2019, respectively. The increase of$6.7 million was primarily due to the following:

--------------------------------------------------------------------------------

Research and development expenses will continue to increase as we continue ourcurrent research programs, initiate new research programs, continue ourpreclinical development of product candidates, and conduct future clinicaltrials for any of our product candidates.

General and administrative expenses

See more here:
BEAM THERAPEUTICS : Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - marketscreener.com

Who’s to blame? These three scientists are at the heart of the Surgisphere COVID-19 scandal – Science Magazine

By Charles PillerJun. 8, 2020 , 7:00 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center.

Three unlikely collaborators are at the heart of the fast-moving COVID-19 research scandal, which led to retractions last week by The Lancet and The New England Journal of Medicine (NEJM), and the withdrawal of an online preprint, after the trove of patient data they all relied on was challenged. The three physician-scientists never were at the same institution nor had they ever before written together, but they are the only authors in common on the disputed papers, and the other co-authors all have ties to at least one of them. Their partnership, which seized a high-impact role during a global public health crisis, has now ended disastrously.

The first author for both retracted papers was cardiac surgeon Mandeep Mehra, an eminent Harvard University professor who works at Brigham and Womens Hospital (BWH) and is known internationally for cardiovascular medicine and heart transplants. He provided the kind of gravitas that can fast-track papers to leading journals. In a statement provided by BWH, Mehra said he had met another of the trio, cardiac surgeon Amit Patel, in academic and medical circles, and that Patel had introduced him to Sapan Desai, a vascular surgeon and founder of Surgisphere, the tiny company that supplied the data. Journal disclosures, however, also indicate Mehra received compensation from Triple-Gene, a gene therapy company Patel co-founded to develop cardiovascular treatments.

Desai publicly aspired to combine big data and artificial intelligence (AI) in ways that he said can replace randomized controlled clinical trials. For a brief moment, it seemed that Surgispheres enticing data set, said to include nearly 100,000 detailed patient records from about 700 hospitals on six continents, would settle questions about the possible benefits of various drugsincluding the controversial antimalarial hydroxychloroquinefor COVID-19 patients.

Patel once apparently headed cardiac surgery at the University of Miami Miller School of Medicine. A university press release announcing his arrival in 2016 is no longer posted on the university website, however, and the school has not confirmed his job duties there. More recently, he has been a volunteer adjunct professor at the University of Utah. But, as STAT first reported yesterday, Patel tweeted on Friday that he had severed his relationship with the university, which a school spokesperson confirmed. In recent years Patel has developed and commercialized experimental stem cell therapies purported to cure heart problems, reverse aging, or treat sexual dysfunction. He is also part of a network of physicians that just launched a trial to use stem cells from umbilical cord blood to treat COVID-19 patients.

Normally co-authors of high-profile papers share subject area expertise or have clear professional ties, says Jerome Kassirer, chief editor ofNEJMduring the 1990s. He calls the collaboration of the apparently disparate individuals completely bizarre, and a red flag that the studies warranted intensive scrutiny that the journals failed to provide.

None of the three co-authors responded to requests for comment. Patel spoke with aSciencereporter initially but said he wanted to wait for audits of the Surgisphere data to comment, and Desais spokesperson stopped communicating after the retractions. Still, interviews with former colleagues and a long paper trail shed some light on each of them.

Desai had a history of convincing respected researchers of his skill and integrity. One of them, Gilbert Upchurch, department of surgery chair at the University of Florida, wrote last year in a journal commentary that he had never met Desai but had nonetheless mentored him remotely and developed an online friendship with him. Upchurch placed the scientist in a group of amazing and talented young vascular surgeons.

Illinois court records show Desai is facing two medical malpractice lawsuits filed last year. He told The Scientist that he deems any lawsuit naming him to be unfounded.

Desai has a history of big aspirations and entrepreneurial venturessome short-lived. His science-fiction blog, corewardfront.com, was meant to find the most parsimonious route for mankind to establish a meaningful presence in space. In 2009, he wrote that the site would publish fiction grounded in facts and reality, adding, the scientific method must be followed religiously. The blog is no longer published.

As a student, Desai won several small National Institutes of Health (NIH) grants for studies of the vestibular system. He started Surgisphere in 2007, when he was a medical resident at Duke University. Surgispheres initial products were medical guides and textbooks, although Desai has said he was working on big data projects for the company from its birth. In 2010, under the firms auspices, he founded the Journal of Surgical Radiologywhose editors included researchers with well-established publishing records. It folded in January 2013. Articles from the journal were cited only 29 times in its history, according to Scimago, a journal rating service. Yet an undated Surgisphere web page, no longer accessible online, said the online-only publication had 50,000 subscribers and nearly 1 million page views monthlywhich would have placed it in elite company in academic publishing.

Surgisphere appears over time to have shifted its efforts into developing a database of hospital records that could be used for research. When the pandemic erupted, Desai declared that his data set could answer key questions about the efficacy and safety of treatments. Speaking about the finding that hydroxychloroquine increases mortality in COVID-19 patients, the main finding from the now retracted Lancet paper, he told a Turkish TV reporter, with data like this, do we even need a randomized controlled trial? Soon after, the World Health Organization temporarily suspended enrolling patients for its COVID-19 trial of the drug.

Immediately after the Lancet and NEJM studies appeared, however, critics identified anomalies in the data. And they doubted that a tiny firmwith a scant public track record in AI, few employees, and no publicly named scientific boardcould convince hundreds of unidentified hospitals in dozens of nations to share complex, protected, and legally fraught patient data. Ultimately, despite Desai promising repeatedly to allow an independent audit of Surgisphere, the firm refused to release the raw patient data and agreements with hospitals for an audit, so no one could validate the authenticity of its database.

No hospitals have come forward to acknowledge working with Surgisphere. Indeed, NHS Scotland, which is mentioned as a case study on the companys website, says none of its hospitals worked with Surgisphere and that it would ask the firm to remove an image of a Glasgow hospital from its website.

Science contacted several of Desais current or former employees or colleagues. Most would not comment. But Fred Rahimi, an Illinois podiatrist and co-author of a paper with Desai, praises the surgeon as highly capable for salvaging limbs, and easy to work with. Through his publicist, Desai cited Mark Melin, a University of Minnesota, Twin Cities, vascular surgeon, as a supporter. Before the retractions, Melin called Desai a gentleman of the highest integrity who has nothing to cover up.

But one physician-scientist who worked closely with Desai several years ago, says, Just about everyone who knew him would say: I just didnt have a good feeling about him. After theyd been with him, most people dissociated themselves from him, the scientist says, declining to be named to avoid personal and institutional embarrassment.

In the decade since completing his medical residency, Desai moved from job to jobat Duke, the University of Texas, Southern Illinois University, and two private Illinois hospitals, according to his LinkedIn profile. You might say we should have stopped him, which now seems obvious, Desais former colleague says. We should have found a way to get together and say, Whats going on here? rather than allowing him to move from place to place. We should have done better as a medical community. We looked the other way.

Before and after his stint at the University of Miami, which appears to have started in late 2016 or early 2017, Patels academic home was the University of Utah. He started as a full-time faculty member at Utah in 2008 and kept that position until he left for Miami. The website for Foldax, a heart valve company that he serves as medical adviser, describes him as a Tenured Professor of Surgery in the Division of Cardiothoracic Surgery at the University of Utah School of Medicine and Director of Clinical Regenerative Medicine and Tissue Engineering at the University of Utah.

The university confirmed Patel had tenure there, but says the directorship was an unofficial title. And among more than 100 publications listed on his University of Utah profile, nearly two-thirds were actually co-authored by other scientists who share the same surname. The page was removed from the university website after inquiries from Science. A university spokesperson said the timing, late Friday last week, was when Patel and the school agreed to separate.

According to the NIH database, Patel has never received funding from the agency. Before the recent COVID-19 papers, one of his most notable publications was a 2016 paper in The Lancet, which reported that extracting stem cells from the bone marrow of a person with end-stage heart failure and then reinjecting them could reduce the number of cardiac events that produced deaths or hospital admissions by 37%. The 126 patient, 31-site, phase II trial was billed in a press release, now not available on the University of Utah website but stored elsewhere, as the largest cell therapy trial for heart failure to date. Despite the apparent positive results, the sponsoring company Vericel no longer is developing stem cells for heart disease and, according to its webpage, is focused on advanced cell therapies for the sports medicine and severe burn care markets.

Patel left Miami under unclear circumstances, but has retained ties with Camillo Ricordi, an influential stem cell researcher at the University of Miami School of Medicine who is also the founder of a nonprofit called the Cure Alliance. The alliance previously focused on testing whether stem cells derived from umbilical cord blood could treat diabetes or Alzheimers, but has now pivoted to fighting COVID-19, according to its website. Ricordi is the principal investigator on a multisite trial to see whether the stem cells can treat lung inflammation in severe COVID-19 patients and Patel is listed in various references to the trial as a key contributor or coprincipal investigator. Ricordi says Patel is an upaid collaborater on the trial and praises Patel's work in regenerative medicine.

Patel recently tweeted that he is related to Dr. Desai by marriage but called that old news and added, Despite this I still do not have the information of what happened at Surgisphere. In addition to apparently connecting Mehra and Desai, Patel had prior connections with other authors of the NEJM paper and the preprint. David Grainger, co-author of the preprint, is a professor of biomedical engineering at the University of Utah and also works with Foldax. Grainger declined to comment.

Timothy Henry, a cardiovascular clinician and scientist at the Christ Hospital in Cincinnati and a co-author on the NEJM article, has written several scholarly articles with Patel, including the 2016 Lancet paper. Henry, who also declined to comment, advises Patels Triple-Gene, which develops cardiovascular gene therapy treatments. Henry and Patel adviseand Patel is a board member ofCreative Medical Technology Holdings, a Phoenix company that develops and markets stem cell therapies, including treatments purported to reverse aging and cure sexual disfunction.

Creative Medicals CaverStem and FemCelz kits are distributed to physicians who use them to extract stem cells from a patients bone marrow, then inject the cells into the penis or clitoral area to stimulate blood flow, according to a statement filed with the U.S. Securities and Exchange Commission. (As of the market close Friday, the publicly traded firms shares were valued at one-third of 1 cent.) The CaverStem treatments are advertised by the company as successful in more than 80% of patients, based on a 40-person phase I clinical trial that was not randomized or controlled, and on observations of 100 other patients. Phase I trials typically measure safety, not health benefits of a potential treatment.

Science contacted multiple colleagues or co-authors of Patel. None would comment. Before the retractions, two high-profile researchersDeepak Bhatt, who directs interventional cardiovascular programs at BWH; and Peter Gruber, a pediatric cardiothoracic surgeon at Yale Universityendorsed Patel on his LinkedIn page. Bhatt says he doesnt know Patel and attempted to remove his endorsement after being contacted by Science. Gruber says he overlapped with Patel at the University of Utah about a decade ago, but doesnt know his work in detail.

In contrast, Mehraauthor of more than 200 scholarly articles, editor ofThe Journal of Heart and Lung Transplantation, and head of the cardiology division of theUniversity of Maryland before moving to BWH in 2012enjoys considerable support even after the unraveling of the recent studies. Obviously, you dont rise to the position hes risen to without being ambitious, but Ive never had any indication whatsoever that he would do anything unethical, says Keith Aaronson, a cardiologist at the University of Michigan, Ann Arbor, who collaborated with Mehra on several studies, including a clinical trial of a mechanical pump for heart failure patients.

Mehra, the first author on both retracted papers, was the only one to issue a personal statement of apology, for failing to ensure that the data source was appropriate for this use. BWH and Harvard declined to say whether further investigation of Mehras roles in the papers would occur. (Mehra has written papers recently with another co-author of the Lancet paper, Frank Ruschitzka of University Hospital Zrich.)

I think he just fell into thisperhaps a little navely, says another former collaborator, cardiothoracic surgeon Daniel Goldstein of the Albert Einstein College of Medicine. Given the amount of data that was in the [Surgisphere] database, its just hard to believe someone would [fabricate] something like this.

Kassirer offers a harsher view: If youre a scientist and youre going to sign on to a project, by God you should know what the data are.

With reporting by Kelly Servick and John Travis.

This story was supported by theScienceFund for Investigative Reporting.

Originally posted here:
Who's to blame? These three scientists are at the heart of the Surgisphere COVID-19 scandal - Science Magazine