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

DetailsCategory: Small MoleculesPublished on Sunday, 10 May 2020 13:30Hits: 566

Improved the Median Time to Disease Progression (37.2 months) vs. Bevacizumab Alone (17.7 months) Following Response to Platinum-Based Chemotherapy with Bevacizumab

Approximately One in Two Women with Advanced Ovarian Cancer Has an HRD-Positive Tumor

KENILWORTH, NJ, USA I May 08, 2020 I AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved LYNPARZA in combination with bevacizumab as a first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Patients will be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

The approval was based on a biomarker subgroup analysis of 387 patients with HRD-positive tumors from the Phase 3 PAOLA-1 trial, which showed that LYNPARZA in combination with bevacizumab reduced the risk of disease progression or death by 67% (HR 0.33 [95% CI, 0.25-0.45]). It improved progression-free survival (PFS) to a median of 37.2 months vs. 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

The most common adverse reactions (ARs) 10% in the overall trial population for PAOLA-1 when treated with LYNPARZA in combination with bevacizumab (N=535) and at a 5% frequency compared to bevacizumab alone (N=267) were fatigue (53% vs. 32%), nausea (53% vs. 22%), anemia (41% vs. 10%), lymphopenia (24% vs. 9%), vomiting (22% vs. 11%) and leukopenia (18% vs. 10%). Grade 3 or above ARs were anemia (17% vs. <1%), lymphopenia (7% vs. 1%), fatigue (5% vs. 2%), nausea (2% vs. 1%), leukopenia (2% vs. 2%) and vomiting (2% vs. 2%). Additional adverse reactions that occurred in 10% of patients receiving LYNPARZA in combination with bevacizumab irrespective of the frequency compared to bevacizumab alone were diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%). Fatal adverse reactions occurred in one patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA in combination with bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA in combination with bevacizumab (5%) than in those receiving bevacizumab alone (1.9%). ARs led to dose interruption in 54% of patients on LYNPARZA in combination with bevacizumab, while 41% of patients on LYNPARZA in combination with bevacizumab had a dose reduction. Discontinuation of treatment due to ARs occurred in 20% of patients on LYNPARZA in combination with bevacizumab.

Approximately one in two women with advanced ovarian cancer has an HRD-positive tumor. For patients with advanced ovarian cancer, the primary aim of first-line maintenance treatment is to delay disease progression for as long as possible.

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre Lon Brard and President of the GINECO group, said, Ovarian cancer is a devastating disease. The magnitude of benefit in HRD-positive patients in the PAOLA-1 trial is impactful. I look forward to seeing this translate into clinical practice.

Dave Frederickson, executive vice president, head of the oncology business unit, AstraZeneca, said, This approval represents another milestone for LYNPARZA in patients with ovarian cancer. The median progression-free survival of more than three years offers new hope for women to delay relapse in this difficult-to-treat disease. These results further establish that HRD-positive is a distinct subset of ovarian cancer and HRD testing is now a critical component of diagnosis and tailoring of treatment for women with advanced ovarian cancer.

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, Advances in understanding the role of biomarkers and PARP inhibition have fundamentally changed how physicians treat this aggressive type of cancer. Todays approval based on the PAOLA-1 trial highlights the importance of HRD testing at diagnosis to identify those who may benefit from LYNPARZA in combination with bevacizumab as a first-line maintenance treatment.

The full results from the Phase 3 PAOLA-1 trial were published inThe New England Journal of Medicine.

Regulatory reviews are currently underway in the European Union, Japan and other countries for LYNPARZA in combination with bevacizumab as a first-line maintenance treatment for patients with advanced ovarian cancer. As part of a broad development program, LYNPARZA is being assessed as a monotherapy and in combination across multiple tumor types.

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

About PAOLA-1

PAOLA-1 is a double-blind Phase 3 trial evaluating the efficacy and safety of LYNPARZA in combination with standard-of-care bevacizumab vs. bevacizumab alone, as a first-line maintenance treatment for advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to first-line treatment with platinum-based chemotherapy and bevacizumab.

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYncologiques) on behalf of GINECO (Groupe dInvestigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specializing in clinical and translational research in patients cancers and a member of the GCIG (Gynecologic Cancer InterGroup).

In the U.S., eligible advanced ovarian cancer patients will be selected for therapy based on the FDA-approved myChoice HRD Plus, an HRD test designed to detect when a tumor has lost the ability to repair double-stranded DNA breaks. Myriad Genetics, Inc. owns and commercializes myChoice HRD Plus.

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About Ovarian Cancer

Ovarian cancer is the fifth most common cause of death from cancer in women in the United States. This year, it is estimated that more than 21,000 women will be diagnosed with ovarian cancer and nearly 14,000 women will die of this disease.

Women with ovarian cancer are often diagnosed with advanced disease, which has a five-year survival rate of about 48%. For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible. BRCA1/2 mutations are found in approximately 22% of all ovarian cancers and approximately 50% of ovarian cancers are HRD-positive.

About Homologous Recombination Deficiency

HRD encompass a wide range of genetic abnormalities, including BRCA mutations, that can be detected using tests. As the BRCA gene drives DNA repair via homologous recombination, mutation of this gene leads to homologous recombination deficiency thereby interfering with normal cell DNA repair mechanisms. BRCA mutations are just one of many HRDs which confer sensitivity to PARP inhibitors including LYNPARZA.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products, including LYNPARZA, the worlds first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Mercks Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit http://www.merck.com/clinicaltrials.

About Merck

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the worlds most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit http://www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

SOURCE: Merck

Read more:
LYNPARZA (olaparib) Approved by FDA as First-Line Maintenance Treatment with Bevacizumab for HRD-Positive Advanced Ovarian Cancer | Small Molecules |...

Based on market cap,CRISPR Therapeutics (NASDAQ:CRSP)ranks as the top biotech focused on developing CRISPR gene-editing therapies. It's more than 2 1/2 times the size ofEditas Medicine (NASDAQ:EDIT) and nearly four times larger thanIntellia Therapeutics (NASDAQ:NTLA).

But based on stock performance so far in 2020, Intellia wins the prize as the hottest CRISPR biotech stock. Its shares have soared more than 40%, thanks in large part to the expansion of its partnership with Regeneron.

While CRISPR Therapeutics and Intellia have captured investors' attention lately, Editas Medicine could now be the CRISPR stock to really watch. There are both near-term and long-term reasons why investors should keep their eyes on this company.

Image source: Getty Images.

In March, Editas and its partner Allerganannounced the dosing of the first patient in a phase 1/2 clinical study evaluating EDIT-101 in treating Leber congenital amaurosis type 10 (LCA10), an inherited form of blindness. Editas CEO Cynthia Collins called it "a truly historic event," as it wasthe world's first human study of anin vivo (inside the body) CRISPR gene-editing therapy.

Editas' Chief Scientific Officer Charlie Albright stated in the company's Q1 conference calllast month that the study "has been cleared to continue based on a review of safety data on the first patient." That's great news, especially considering the pioneering nature of the LCA10 therapy.

I don't necessarily look for this clinical trial to provide a big catalyst for Editas over the next few months, at least not directly. But it could give the biotech an indirect catalyst.

Editas Medicine's experience with EDIT-101 in targeting LCA10 has enabled it to move forward with EDIT-102, a CRISPR therapy targeting another genetic eye disease, Usher syndrome 2A. Allergan is currently reviewing a preclinical data package for the potential licensing of EDIT-102. Editas expects a decision from Allergan on exercising its option for EDIT-102 by the third quarter of 2020.

My hunch is that Allergan will decide to license EDIT-102 unless some safety issue emerges in the phase 1/2 study for EDIT-101. A positive decision would likely cause Editas' shares to jump.

CRISPR Therapeutics is the leader in developing a CRISPR therapy for treating rare blood diseases sickle cell disease and beta-thalassemia. The company and its partner, Vertex Pharmaceuticals, expect to report additional data from two phase 1/2 studies in progress evaluating CRISPR/Cas9 gene-editing therapy CTX001 later this year.

Editas is behind CRISPR Therapeutics right now. But I won't be surprised if Editas emerges as a winner in sickle cell disease and beta-thalassemia over the long term.

The company plans to file for FDA approval by the end of 2020 to begin clinical testing of EDIT-301 in treating sickle cell disease. EDIT-301 uses its proprietary enzyme Cas12a (also known as Cpf1) instead of Cas9, the enzyme most commonly used in CRISPR gene-editing therapies.

Editas thinks that EDIT-301 could be the best-in-class CRISPR therapy for treating both sickle cell disease and beta-thalassemia. One reason behind the biotech's confidence is that the therapy edits the HBG1 and HBG2 genes rather than theBCL11Ae gene targeted by CRISPR Therapeutics' CTX001. Editas believes that this difference will give EDIT-301 a better safety profile than CTX001 will have. The company also thinks that using Cas12a will lead to sustained higher fetal hemoglobin levels than using the Cas9 enzyme will.

There's another intriguing possibility for Editas Medicine. Its partner on EDIT-101, Allergan, was recently acquired by AbbVie (NYSE:ABBV). The primary reason for this deal was for AbbVie to reduce its dependence on Humira, which faces biosimilar competition in the U.S. beginning in 2023.

AbbVie has other arrows in its quiver for offsetting the inevitable loss of revenue from Humira -- notably including its new immunology drugs Rinvoq and Skyrizi. However, the closer the date approaches for Humira's U.S. sales decline, the more I suspect that AbbVie will be interested in making additional smaller deals to boost its top line.

If EDIT-101 is successful in phase 1 testing and advances to phase 2, Editas Medicine could very well be on AbbVie's acquisition radar. The biotech wouldn't be so expensive that it would require AbbVie to take on a lot of additional debt. Buying Editas could also boost AbbVie's oncology program since Editas has several preclinical programs that use CRISPR gene editing in cancer cell therapies.

To be sure, Editas Medicine is a speculative play. For that matter, so are CRISPR Therapeutics and Intellia Therapeutics. All of these biotech stocks face significant risks that their gene-editing therapies won't work or won't be safe. But the possibility of near-term catalysts and the tremendous long-term potential for Editas make this CRISPR biotech one for investors to closely watch.

See original here:
Why Editas Medicine Is Now the CRISPR Stock to Really Watch - Motley Fool

Rosaly CORREA-DE-ARAUJO, Senior Scientific Advisor to the Director, DGCG,Division of Geriatrics and Clinical Gerontology (DGCG).

Maintaining the ability to walk without assistance and perform daily activities is essential for health and independence as we age. Conducted from 2010 to 2013, the NIA-supported Lifestyle Interventions and Independence for Elders (LIFE) study examined whether a long-term structured physical activity program was more effective than a health education program in reducing the risk of major mobility disability in sedentary older adults. LIFE showed that a structured physical activity program a goal of walking 150 minutes per week plus strength, flexibility and balance training reduced the risk of mobility loss and death.

LIFEs impressive accomplishments were summed up in a review article and further discussed in an editorial. Its findings that following the physical activity program for an average of 2.6 years reduced mobility loss risk by 18 percent have shaped several U.S. and international recommendations for physical activity in older adults, including the Physical Activity Guidelines for Americans.

Now, 7 years after the study ended, data from LIFE is continuing to advance the field. A treasure trove of data from the LIFE study is available from the NIA AgingResearchBiobank. The availability of these samples and data presents considerable scientific and clinical opportunities for trainees, junior and senior investigators, and clinicians who can use LIFEs biospecimens and related data to answer additional research questions that go beyond those related to maintaining independence and mobility as we age.

In the past year, the AgingResearchBiobank has distributed more than 17,000 LIFE biospecimens and related study data to qualified researchers. LIFE samples and data are being used in ongoing investigations in the U.S. and abroad. These are just a few examples of the exciting projects now underway:

LIFE is a great example of the type of wellcoordinated, rigorously conducted randomized trial that NIA supports. NIA is committed to building and sharing these quality data and sample resources as we work to advance evidence-based medicine and improve the well-being of older adults. Please visit the AgingResearchBiobank online and let us know if you have questions or comments below!

See the article here:
After LIFE: Thanks to AgingResearchBiobank, groundbreaking study data continues to inspire us - National Institute on Aging

Medical staff at Lehigh Valley Hospital - Hazleton hold up signs, congratulating a COVID-19 patient being sent home.

Submitted photo

While it may seem as though there is only bad news about COVID-19, medical professionals from two hospitals say there are some things to be cautiously optimistic about as the battle against the virus rages on.

Dr. Jodi Lenko, vice chair for the department of medicine at Lehigh Valley Hospital Hazleton, and Dr. Alvin Sharma, a critical care specialist at Geisinger Community Medical Center and Geisinger Wyoming Valley, both suggested one of the most heartwarming things about this is watching how medical teams have come together to serve the community.

Overall, the group effort and the camaraderie of the staff, I think thats the general theme, Lenko said. Everyone has really pulled together and taken on responsibilities that they didnt have 24 hours before.

Sharma agreed.

Even with the stress (of the virus), theres an incredible energy thats come out of this: teamwork, collaboration and working alongside each other, he said.

Lenko said she has worked at numerous different levels of the response, being actively involved with the setting up of an outdoor testing site at her Hazleton hospital and working in the intensive care unit for much of last week.

From her point of view, she said there are a few reasons to hope for the best.

Were cautiously optimistic, she said. About a week and a half ago, we saw the peak of in-patient numbers, but weve seen a steady plateau.

This could indicate the beginning of a positive trend; while the amount of people hospitalized for COVID-19 complications has stayed steady at Lehigh Valley Hospital Hazleton, that number has not continued on the upward trajectory it was on.

Im hopeful we arent going to hit the catastrophic level we were fearful of, she said. Hopefully were starting to see stability.

Lenko did emphasize, though, that so far, it is only a slight trend in the positive direction.

That said, though, both Sharma and Lenko said there have been some remarkable successes in regards to critically-ill patients.

The main thing that we all should hear is that weve had successes, weve had patients survive and go home, weve had patients who were severely critically ill survive and go home, Sharma said.

Lenko said shes seen some remarkable successes in the ICU. She said that, so far, its been incredibly hard to get patients off ventilators once they have had to go on them. However, she said that, so far, around five patients have been able to have their breathing tubes removed, and one of them has even gone home.

She said she took care of one critically-ill patient for seven days, and when medical staff was finally able to remove his breathing tube, the patient thanked her profusely.

It brought tears to my eyes, Lenko said. Its a small little victory everyone takes great pride in those victories.

Both Lenko and Sharma made it clear that these victories, no matter how small, would not be possible without the tireless work of a whole team of individuals.

The nursing staff, the respiratory therapists, the emergency room physicians, the multiple-disciplinary teams have all worked together and truly stepped up to the challenge, Sharma said. This energy that has developed has allowed us to create innovative preparedness.

Sharma specifically wanted to thank the work of Stephanie Rarig and Chad Cope, both ICU nurse operations managers at the hospitals he worked at, and pulmonologist Dr. Paul Arkless.

Its tiring, but its a joy, Sharma said of the work he and the rest of the team are doing.

Perhaps the most positive news, though, isnt news at all. Its been reported all along that the majority of people who come down with COVID-19 are able to recover at home if they carefully monitor their symptoms, and so far, that remains true, Lenko said.

A majority of people will be recovering from home, she said. We are seeing lots of patients recover. Ive written three or four back-to-work notes this week.

Reach Patrick Kernan at 570-991-6386 or on Twitter @PatKernan

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Medical professionals: some positive progression in the fight against COVID-19 - Wilkes Barre Times-Leader

ANI | Updated: Apr 26, 2020 22:08 IST

Washington D.C. [USA], April 26 (ANI): In a new discovery, scientists have found the protein that is responsible for helping the human heart heal.A group of scientists from the UT Southwestern Medical Center scientists have discovered a protein that works with other proteins during development to put the brakes on cell division in the heart and helps it to heal.The research was published in the journal-Nature.The findings could eventually be used to reverse this developmental block and help heart cells regenerate, offering a whole new way to treat a variety of conditions in which heart muscle becomes damaged, including heart failure caused by viruses, toxins, high blood pressure, or heart attacks.Current pharmaceutical treatments for heart failure - including ACE inhibitors and beta blockers - center on trying to stop a vicious cycle of heart muscle loss as strain further damages remaining heart muscle, causing more cells to die, explains UT Southwestern physician-researcher Hesham A. Sadek, M.D., Ph.D., a professor of internal medicine molecular biology, and biophysics. There are no existing treatments to rebuild heart muscle.Nine years ago, Sadek and his colleagues discovered that mouse hearts can regenerate if they're damaged in the first few days of life, spurred by the division of cardiomyocytes, the cells responsible for a heart's contractile force.However, this capacity is completely lost by 7 days old, an abrupt turning point in which division of these cells dramatically slows and the cells themselves enlarge. The reasons why these cells gradually slow and stop dividing has been unclear.Sadek and his team discovered in 2013 that a protein called Meis1, which falls into a category known as transcription factors that regulate the activity of genes, plays a key role in stopping heart cell division.However, he explains, although deleting this gene in mice extends the window of heart cell division, this effect is transient - heart cells missing this gene eventually slow and stop their multiplication.Consequently, the researchers wondered whether there were redundant mechanisms in place that stop heart cell division even when Meis1 is absent. Toward that end, they looked to see what other transcription factors might track activity with Meis1 in heart cells as they rapidly divide and then slow to a halt in the days after birth.They quickly discovered one called Hoxb13 that fit the bill. Other proteins in the Hox family, Sadek notes, have been shown to act as chaperones to Meis1 in other types of cells, ferrying Meis1 into the cell nucleus.To better understand Hoxb13's role in heart cells, the researchers genetically engineered mice in which the gene that codes for Hoxb13 was deleted. These mice behaved much like those in which just the gene for Meis1 was deleted - the window for heart cell rapid division was increased but still closed within a few weeks.When the researchers shut off Hoxb13 in adult mouse hearts, their cell division had a brief resurgence, enough to prevent progressive deterioration after an induced heart attack but not enough to promote significant recovery.However, when the researchers deleted both the genes for Meis1 and Hoxb13, heart cells in these mice appeared to revert to an earlier stage in development, both decreasing in size and multiplying more. After an induced heart attack, these mice had a rapid improvement in the amount of blood each beat could expel from the heart. Their heart function had almost returned to normal.With clear evidence that Meis1 and Hoxb13 work together to stop heart cell division in the days after birth, Sadek and his colleagues looked for what might in turn regulate these proteins. Their experiments suggest that the answer is calcineurin, a protein that's responsible for regulating the activity of other proteins by removing their phosphate groups.Because calcineurin plays a key role in a variety of diseases and other medical conditions, such as rheumatic arthritis, schizophrenia, diabetes, and organ transplant, several drugs already exist on the market that target this protein.Conceivably, says Sadek, other drugs could be developed to directly target Meis1 and Hoxb13. Researchers may eventually be able to develop strategies to restart heart cell division through a single drug or combinations that target any part of this regulatory pathway, he adds."By building up the story of the fundamental mechanisms of heart cell division and what blocks it. We are now significantly closer to being able to harness these pathways to save lives," Sadek said. (ANI)

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Researchers find a protein that helps heart heal - ANI News

While researchers are working to advance drugs to treat COVID-19 and vaccines to give people immunity against the virus, the mental health impact of the pandemic will also have to be managed. This is where PGx testing may be most useful, experts in the field said.

"It is worthwhile to consider not just the utility of PGx in preventing hospitalization or changing the course of COVID-19 care," but also the impact it could have on managing "the burden on the patients that do survive a COVID-19 infection [and] those that are suffering from the isolation of social distancing, as well as the financial hardships," said David Thacker, a clinical pharmacogenetics content specialist at Translational Software.

According to a recent JAMA editorial, during the SARS outbreak in 2003, there was a greater incidence of post-traumatic stress syndrome and psychological distress among patients and doctors. In communities impacted by Hurricane Ike in 2008, around 5% of individuals met the criteria for major depressive disorder, while one in 10 adults in New York City had symptoms of the disorder after 9/11.

"In the context of the COVID-19 pandemic, it appears likely that there will be substantial increases in anxiety and depression, substance use, loneliness, and domestic violence; and with schools closed, there is a very real possibility of an epidemic of child abuse," wrote Sandro Galea from Boston University School of Public Health, Raina Merchant from the Perelman School of Medicine, and Nicole Lurie from the Coalition for Epidemic Preparedness Innovations in Norway.

A survey in March by the American Psychiatric Association found that more than a third of polled individuals said that the pandemic was seriously impacting their mental health, nearly half said they were scared about getting the virus, and 62% said they feared a loved one would get it. Meanwhile, calls to substance abuse and mental health help lines increased eightfold from February to March.

As the pandemic continues, people may increasingly turn to medications to deal with the psychological wounds left by the pandemic. Drugs to treat mental health conditions, including major depressive disorder, are some of the most widely prescribed drugs in the U.S., but they're also highly variable and associated with unwanted side effects.

As such, one of the main areas where PGx testing has seen uptake is for personalizing psychiatry drugs. Myriad Genetics recently published a meta-analysis involving more than 1,500 patients with major depressive disorder who were enrolled in four studies, which showed that patients who received treatment based on PGx information had significantly better outcomes than those who did not.

Although PGx testing in psychiatry is not without its naysayers, doctors may reach for such testing if the use of mental health drugs increases during or after the pandemic. Genomind, a mental health-focused PGx testing company, recently took a number of steps to make it easier for physicians to deliver psychiatric care during the pandemic. Doctors can order Genomind's PGx test and send a saliva collection kit to patient's homes, which can then be mailed to the lab for analysis. Through Genomind, doctors also have access to Sharecare's HIPAA-compliant telemedicine platform for free until September, which they can use to remotely see patients and discuss PGx test results, if ordered.

"The utility of PGx during the COVID-19 crisis is more important than ever," a spokesperson for the company said. "This service is helping enable critical mental health treatment during the pandemic and Genomind is doing its best to enable as many mental health professionals as possible."

This story first appeared in our sister publication, Genomeweb.

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Drug-gene testing could give experts insight into COVID-19 treatment - ModernHealthcare.com

Genetic variants that are unrelated to the IOP are associated with a family history of glaucoma and play a role in the onset of primary open-angle glaucoma (POAG). Genetic variants that are related to the IOP are associated with the age at which glaucoma is diagnosed and are associated with disease progression.

What is known about POAG, the most prevalent form of glaucoma, is that increased IOP and myopia are risk factors for damage to the optic nerve in POAG.

Related: Stent offers IOP stability more than three years after surgery

A family history of glaucoma is a major risk factor for development of POAG, in light of which, therefore, genetic factors are thought to be important in the disease pathogenesis and a few genes mutations have been identified as causing POAG, according to Fumihiko Mabuchi, MD, PhD, professor, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Kofu, Japan.

Myopia has been shown to be a risk factor for POAG in several studies. However, it can be difficult to diagnose true POAG in myopic patients and controversy exists over whether it is real risk factor.

Myopic optic discs are notoriously difficult to assess, and myopic patients may have visual field defects unrelated to any glaucomatous process.

The prevalence of POAG increases with age, even after compensating for the association between age and IOP.

Related: Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows

Part of the storyDr. Mabuchi and his and colleagues, recounted that these factors are only part of the story.

According to Dr. Mabuchi and his colleagues, cases of POAG caused by these gene mutations account for several percent of all POAG cases, and most POAG is presumed to be a polygenic disease.

Recent genetic analyses, the investigators explained, have reported genetic variants that predispose patients to development of POAG and the additive effect of these variants on POAG, which are classified as two types.

The first genetics variants are associated with IOP elevation.

Related: Sustained-release implant offers long-term IOP control, preserved visual function

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Genetic variants linked with onset, progression of POAG - Ophthalmology Times

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CRISPR corrects genetic defect so cells can normalize blood sugar

Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome.

Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

The study is published online April 22 in the journal Science Translational Medicine.

Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

A few years ago, Millman and his colleagues discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, those same researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared quickly in mice with the CRISPR-edited cells implanted beneath the skin, and the animals blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Their newly implanted beta cells could produce insulin, just not enough to reverse their diabetes.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

In the future, using CRISPR to correct certain mutations in beta cells may help patients whose diabetes is the result of multiple genetic and environmental factors, such as type 1, caused by an autoimmune process that destroys beta cells, and type 2, which is closely linked to obesity and a systemic process called insulin resistance.

Were excited about the fact that we were able to combine these two technologies growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects, Millman said. In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making induced pluripotent stem cells from blood and they are working on developing stem cells from urine samples.

In the future, Urano said, we may be able to take a few milliliters of urine from a patient, make stem cells that we then can grow into beta cells, correct mutations in those cells with CRISPR, transplant them back into the patient, and cure their diabetes in our clinic. Genetic testing in patients with diabetes will guide us to identify genes that should be corrected, which will lead to a personalized regenerative gene therapy.

Maxwell KG, Augsornworawat P, Velazco-Cruz L, Kim MH, Asada R, Hogrebe NJ, Morikawa S, Urano F, Millman JR. Gene-edited human stem cell-derived cells from a patient with monogenic diabetes reverse pre-existing diabetes in mice. Science Translational Medicine, published online April 22, 2020.

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of General Medical Sciences, the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH). Grant numbers R01 DK114233, DK112921, TR002065, TR002345, T32 DK108742, R25 GM103757, T32 DK007120, P30 DK020579, P30 CA91842, UL1 TR000448 and UL1 TR002345. Additional assistance was provided by the Washington University Genome Engineering and iPSC Center, the Washington University Diabetes Center, and the Washington University Institute of Clnical and Translational Science, with additional funding from the JDRF, the Washington University Center of Regenerative Medicine, startup funds from the Washington University School of Medicine Department of Medicine, the Unravel Wolfram Syndrome Fund, Silberman Fund, Stowe Fund, Ellie White Foundation for Rare Genetic Disorders, Eye Hope Foundation, Snow Foundation, Feiock Fund, Childrens Discovery Institute, Manpei Suzuki Diabetes Foundation, and a JSPS Overseas Research Fellowship.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Diabetes reversed in mice with genetically edited stem cells derived from patients - Washington University School of Medicine in St. Louis

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Another COVID-19 Vaccine Looks Promising

According to the World Health Organization, there are 70 vaccines being developed worldwide for COVID-19, with three already in human clinical trials. The furthest along is one by CanSino Biologics and the Beijing Institute of Biotechnology, which is in Phase II. The others are by U.S. companies, Inovio Pharmaceuticals and Moderna. Another institution, the University of Pittsburgh, also announced that in laboratory tests their COVID-19 vaccine, delivered via a fingertip-sized patch, showed positive results in laboratory mice, producing antibodies specific to SARS-CoV-2 at enough amounts to neutralize the virus. The research was published in EBioMedicine, published by The Lancet.

We had previous experience on SARS-CoV in 2003 and MERS-COV in 2014, said co-senior author Andrea Gambotta, associate professor of surgery at the Pitt School of Medicine. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We know exactly where to fight this new virus. Thats why its important to fund vaccine research. You never know where the next pandemic will come from.

It uses a more traditional process than the mRNA one being used by Moderna. The virus is being called PittCOVacc, and uses laboratory-manufactured pieces of viral protein to build immunity. Its a process similar to that used in seasonal flu shots. They also leveraged a new technique to deliver the drug, called a microneedle array, to increase the potency of the vaccine. The fingertip-sized patch has 400 tiny needles that deliver the spike protein pieces into the skin. It goes on like a Band-Aid. The needles are built from sugars and the antigens, and they just dissolve.

We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient, said Louis Falo, co-senior author and professor and chair of dermatology at Pitts School of Medicine and UPMC. And its actually pretty painlessit feels kind of like Velcro.

They are currently submitting an Investigational New Drug (IND) with the U.S. Food and Drug Administration (FDA) and hope to begin Phase I human clinical trials in the next few months.

Genetic Mechanisms of Inflammatory Bowel Disease

Researchers at Children's Hospital of Philadelphia identified a genetic variant that causes the development of inflammatory bowel disease (IBD). The pathway is linked to other immune disorders. More than 240 genetic regions are already associated with IBD, but each region has multiple markers and not all are causative. The researchers focused on the single nucleotide polymorphism (SNP) rs1887428, located on the promoter region of the JAK2 gene. The protein coded by the gene controls the production of blood cells. The team found that two transcription factors, RBPJ and CUX1, recognize the DNA sequence altered by the rs1887428 SNP, and while it only has mild influence on JAK2 expression, it was amplified by other proteins in the JAK2 pathway.

Possible Mechanism of Link Between Obesity and Breast Cancer

Breast cancer (and other cancers) and obesity are associated, but the reason for that link isnt well understood. Researchers from the University of Louisville published research suggesting that the fatty acid binding protein family, especially FABP4, plays a critical role. Fat tissue produces FABP4 within fat cells, which processes and distributes water-insoluble long-chain fatty acids. Normally, some FABP4 enters the bloodstream, but the higher fat volume, the more FABP4 is secreted. They believe two mechanisms are in play. Within cells, FABP4 increases in certain tumor-associated macrophages, which accumulate in tumors and promote cancer growth. And second, when elevated levels of FABP4 circulate outside the fat cells, it promotes breast cancer by directly interacting with breast cancer cells.

Using Cellular Machinery Without the Cells to Develop Drugs

Northwestern University and ShanghaiTech University leveraged cell-free synthetic biology to produce a drug that kills SARS-CoV-2 in cell cultures. They indicate they could create the new drug by taking the molecular machinery out of cells and using that machinery to make a product in a safe, cheap and quick way. The molecule is called valinomycin. By using this method, they were able to increase production yields more than 5,000 times in only a few quick design cycles.

Glucose Metabolism Linked to Alzheimers Disease

Researchers with the National Institutes of Healths National Institute on Aging conducted the largest study so far on proteins related to Alzheimers and identified proteins and biological processes that regulate glucose metabolism that are associated with Alzheimers. The study was published in the journal Nature Medicine.

The study was part of the Accelerating Medicines Partnership for Alzheimers Disease (AMP-AD). The investigators assayed the levels and analyzed the expression patterns of more than 3,000 proteins in brain and cerebrospinal fluid samples collected at centers across the U.S.

This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimers disease, said Richard J. Hodes, NIA director. This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources.

The study involved analyzing protein expression patterns in more than 2,000 human brain and almost 400 cerebrospinal fluid samples taken from both healthy individuals and Alzheimers patients. They analyzed how the protein modules relate to Alzheimers and other neurodegenerative diseases. They observed changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain tissues from both Alzheimers patients and people with documented brain pathology who were cognitively normal. This also would seem to support increasing evidence that brain inflammation is involved in the disease as well.

In Alzheimers patients, they found that how cells extract energy from glucose is increased in both the brains and spinal fluid of Alzheimers patients. The proteins observed were also elevated in preclinical Alzheimers patients, which is to say, people with brain pathology of the disease who had not shown cognitive decline.

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Research Roundup: Another Promising COVID-19 Vaccine and More - BioSpace

Evotec is building a gene therapy R&D center manned by ex-Takeda scientists and has already landed a multi-year drug discovery pact for it with their former Japanese employer.

Evotecis expanding into the field of gene therapy by building an R&D center in Austria using scientists previously employed by Takeda, whose first project will be a long-term research and discovery project with their former Japanese employer, exploring oncology, rare diseases, neuroscience and gastroenterology.

The entry by the German discovery alliance and development partnership group into gene therapy further expands its capabilities beyond small molecules, cellular therapies and biologics while the research alliance withTakeda Pharmaceutical, announced on 6 April, builds upon an existing collaboration begun last September around drug discovery programs in which Evotec will deliver clinical candidates for Takeda to pursue into clinical development.

Image: iStock/sittithat tangwitthayaphum

This addition of gene therapy is the latest step in a very long strategy at Evotec to build a truly comprehensive organization which can deliver medicines discovery and development right across the different modalities, or scientific tools, that we see in modern medicine today, Evotec chief operating officer Craig Johnstone toldScrip.

He said the move was consistent with Evotecs two-pronged drug discovery strategy, which uses the Hamburg-based groups so-called Execute segment allying with external pharma partners which in turn supports reinvestment into Evotecs internal pipeline within its so-called Innovate segment.

This allows us to bring gene therapy project concepts into the Evotec Innovate pipeline at our choice and discretion. That was not possible before, so we can now use gene therapy to support our partners and also use it to support ourselves.

Johnstone said Evotec already makes broad use of CRISPR in its discovery and development activities. This will only amplify that aspect of Evotecs activities, he added.

Evotec Gene Therapy (Evotec GT) will start operations with a team of gene therapy experts at an R&D site in Orth an der Donau, Austria. Its scientists have deep expertise in vectorology and virology as well as disease insights, in particular in hemophilia, hematology, metabolic and muscle diseases.

We are recruiting the team, which will be composed of ex-Takeda employees. Its leadership has a long history in gene therapy stretching back years and to legacy organizationsBaxaltaandShire which were acquired by Takeda, but who were made redundant. Well be bringing them all on board over the next eight weeks, Johnstone said. Friedrich Scheiflinger, previously head of drug discovery for Takeda in Austria, will head up the new gene therapy unit.

No financial details were disclosed about Evotecs latest collaboration with Takeda.

Its a fairly straight-forwardcontractual framework that has been agreed between Evotec and Takeda, Johnstone said, without elaborating.

Sten Stovall is a London-based editor and writer with 40 years of experience in the field of journalism, including more than 20 years with Reuters and eight years with The Wall Street Journal/Dow Jones Newswires. He can be reached at sten.stovall@informa.com

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Evotec extends Takeda pact to gene therapy - Bioprocess Insider - BioProcess Insider

Money is on the way. At least that's the case if you're among the 80 million Americans who qualify for the coronavirus stimulus checks funded by theCoronavirus Aid, Relief, and. Economic Security (CARES) Act signed into law last month.

For too many, the $1,200 payment will be needed simply to make ends meet. Others, though, will have extra money to spend or to invest. If you're in the latter group, investing your stimulus check makes a lot of sense with the stock market still down by a double-digit percentage from the highs set earlier this year.

But which stocks are great picks that could generate explosive growth over the next several years? Here are three stocks to buy to get a big bang for the buck with your coronavirus stimulus check.

Image source: Getty Images.

Shares of MongoDB (NASDAQ:MDB) sank as much as 45% in mid-March before bouncing back nicely. But the stock is still down well below its previous highs. I think buying MongoDB now will enable patient investors to reap tremendous gains over the long run.

The last two letters of MongoDB's name reveal the company's focus on the database market. But MongoDB's database is different from the big players in the industry in a couple of important ways. First, it was designed from the ground up for the unstructured data that's being generated in massive quantities today, like images and videos. Second, MongoDB created its database to be run from anywhere, including the cloud.

I really like the first part of the company's name, though, because it hints at the size of the opportunity that lies ahead. "Mongo" is short for "humongous." And MongoDB definitely has a humongous opportunity. The global database market is expected to grow to $97 billion by 2023 from $71 billion this year. MongoDB currently captures less than 1% of the market, but it's growing faster than its much larger rivals.

A major key to MongoDB's success is its Atlas cloud-based database-as-a-service. The company reported 80% year-over-year sales growth for Atlas in Q2, with the fully managed cloud database now generating 41% of MongoDB's total revenue. I expect Atlas will continue to fuel MongoDB's tremendous growth and help the company snag a lot more of the expanding global database market over the next five years.

Fastly's(NYSE:FSLY) name also hints at what the company does -- delivering web content to users faster than other technologies. The company's platform moves data and applications closer to users at the edge of the network, the point right before an organization loses control of its data.

You could also say that the company's name describes its own growth. Fastly reported 44% year-over-year revenue growth in the fourth quarter of 2019. Its number of enterprise customers in Q4 increased to 288 with an average spend of $607,000, up from 274 enterprise customers in Q3 with an average spend of $575,000.

The edge cloud platform and content delivery network technology offered by Fastly will almost certainly enjoy even greater demand in the future with the rise of 5G wireless networks. While major cloud services providers including Amazon.comand Microsoftwill compete against Fastly, the growth in the overall market should be enough for multiple winners.

Fastly stock now trades at a double-digit percentage discount from earlier this year. It's still expensive based on conventional valuation metrics but with its strong growth prospects, I think this tech stock will be a winner over the long term.

In keeping with our theme of what's in a name,Editas Medicine (NASDAQ:EDIT)also picked its corporate name to indicate the business it's in. The company is a leader in the development of gene-editing therapies that use CRISPR, a method of gene editing that has been hailed as the biotech discovery of the century.

Unlike MongoDB and Fastly, Editas can't boast of impressive revenue growth yet. That's because the company is still several years away from the possibility of winning regulatory approval for its first drug. But Editas is making progress toward the goal of launching its first product.

In March, Editas and its partner, Allergan, dosed the first patient in the world's first clinical study in humans evaluating an in vivo (inside the body) CRISPR gene-editing therapy. This study will assess the safety, efficacy, and tolerability of a CRISPR therapy targeting Leber congenital amaurosis type 10 (LCA10), the most common cause of genetic childhood blindness.

Editas is also working on advancing a promising CRISPR therapy for treating rare genetic disorder sickle cell disease and hopes to file for approval by the end of 2020 to begin a clinical study. It's also developing an experimental CRISPR therapy for treating solid tumors. The biotech stock is the riskiest of these three, but if Editas is successful with its gene-editing programs it could potentially be the biggest winner of all.

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3 Stocks to Buy to Get a Big Bang for the Buck With Your Coronavirus Stimulus Check - The Motley Fool

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women - BMC Blogs Network

Andre Watson

SAN FRANCISCO (PRWEB) June 18, 2020

Vaccines currently in development face the dual challenge of overcoming the temporary immunity presented by coronavirus infection, and the SARS-CoV-2 viruss highly effective cloaking mechanism that effectively renders it invisible to the immune system.

Ligandals technology has been designed around the unique genetic signature of the virus, which has informed the development of a peptide nanoscaffold. This peptide prevents the virus from binding with human cells, halting infection. The peptide also simultaneously disables the viral cloaking mechanism, making the virus vulnerable to an immune response.

Andre Watson, CEO and Founder of Ligandal, says, I started Ligandal to create practical genetic medicine technology that solves the worlds most pressing health problems. We had been developing a way of training T-cells to attack cancer tumours, but when the COVID-19 pandemic began, I realised our technology would be effective at neutralising this single, virulent pathogen without requiring a gene therapy component. The beauty of our solution is that it can be used as treatment and vaccine. In infected people, the peptide will prevent viral entry and replication, while bolstering the immune response and formation of neutralising antibodies that can eliminate the virus. Other approaches may neutralise the virus, but many alternatives such as antibody therapies and viral-neutralising compounds will leave the body vulnerable to repeat infection. In those who havent been infected, the peptide will display critical immunoepitopes for antibody and T cell responses against the key parts of the virus necessary for forming a neutralising response. The peptide can also be used in conjunction with other treatments and vaccinesand may bolster the efficacy of spike protein vaccines in particularalthough that shouldnt be necessary if we achieve in vivo results suggested by the in silico modelling.

Adam Hamdy, a medical consultant and author, who recently joined the companys advisory board, says, The microbiological characteristics of SARS-CoV-2 make it extremely unlikely that current vaccine approaches, which rely on training the immune system but present key challenges with this virus, will offer anything more than partial protection at best. It was clear to me that any effective response to this virus had to target it directly while also bolstering immune response.

Importantly, Ligandals peptide has advantages over other technologies in development because it is room temperature stable, meaning it represents a genuinely global solution, both in terms of logistics and the storage of the medicine. It also has a low cost per dose once at mass production scale, which means global producton is entirely feasible. It can also move rapidly through preclinical and clinical studies given the accelerated global regulatory environment and simple at scale manufacturing process.

Andre Watson says, As hostile actors take note of the havoc caused by the SARS-CoV-2 virus, it is clear we need better ways to ramp up our biodefense capabilities. A rapid four-year conventional vaccine cycle to trial a single solution isnt going to be sufficient to meet future threats. Ligandal modelled its peptide within five hours of receiving a genetic sequence of the virus, and was ready to test its response in two months. We anticipate being ready to commence clinical studies later this year or very early next year. Our only limitation in getting this to the general public is how quickly we can move through the clinical studies.

Adam Hamdy says, A long term solution to the COVID-19 problem lies in genetic medicine. Ligandals peptide is an exciting leap forward in our ability to address and neutralise the virus directly. Unlike conventional vaccines, which only get one shot at proving efficacy, Ligandals peptide can be improved by rewriting its genetic code in response to novel viral variants, giving us the opportunity to rapidly iterate and keep at the problem until we get the answer absolutely right.

About Ligandal

Based in San Francisco, Ligandal is a genetic medicine company that uses nanotechnology to develop targeted and personalised therapies.

For more information visit http://www.ligandal.com

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Genetic Medicine will be the Solution to COVID-19, and Ligandal is Leading the way - PR Web

Newswise Pancreatic cancer is expected to become the second-deadliest cancer in the United States by 2030, driven in part by rising obesity rates. A new study led by Yale Cancer Center (YCC) researchers has demonstrated in mice that hormones released from the pancreas itself can advance pancreatic cancer and that weight loss can stop this process in its early stages. The research was published today in the journal Cell.

These discoveries raise the hope of finding new ways to prevent both the growth and the spread of pancreatic cancer, said Mandar Muzumdar, M.D., assistant professor of genetics at Yale School of Medicine, a member of the Yale Cancer Biology Institute, and senior author of the paper.

Muzumdar and his collaborators, including a team from the Massachusetts Institute of Technology (MIT), began the project with a mouse model that was genetically modified to develop pre-cancerous pancreatic lesions with a mutation in the KRAS gene, which is mutated in most human pancreatic cancers. The mice were also genetically engineered both to become obese and to rapidly lose weight when scientists administered an additional form of genetic manipulation or limited their food intake.

Unlike mice of normal weight engineered with the KRAS mutation, obese mice with this mutation rapidly developed advanced pancreatic cancer. And unlike most humans diagnosed with the disease, tumors in the model mice did not present additional genetic mutations that would further enable tumor progression. Just by making them obese, we could essentially simulate the effect of an additional mutation, Muzumdar said. That suggested that there is a huge effect of obesity on cancer development in mice.

Next, he and his colleagues studied whether weight loss could slow the development of cancer in the mice who had developed pre-cancerous lesions. The results were dramatic. We found that if we made the mice lose weight prior to advanced cancer development, we could essentially block the progression to advanced cancer almost as if they were never obese, Muzumdar said. If we made the mice lose weight after advanced cancers had developed, the mice still succumbed to the disease within the same timeframe.

The finding suggested the possibility of intercepting tumor formation or progression by weight loss, or eventually using novel drugs that target the underlying biological pathways. Muzumdar noted that the result matches up well with clinical studies of people who are given weight-reducing bariatric surgery, which appears to lower the risk of developing pancreatic cancer.

To determine the cause of the tumors in these mice, the team looked at the genes being expressed in clusters of hormone-producing cells called islets in their pancreases. One type of pancreatic islet cell known as a beta cell normally produces insulin. In these mice, however, some beta cells were churning out a hormone called cholecystokinin (Cck), normally generated in the intestine to aid digestion. These beta cells also seemed to secrete less insulin. This finding interested Muzumdar and his team because they knew that the Cck hormone acts on the digestive enzyme-secreting cells where the predominant type of pancreatic cancer emerges.

They also discovered that Cck expression in the islets dropped when the obese mice lost weight. Additionally, other mouse models that were engineered with the KRAS mutation and forced to express Cck in beta cells, but were not obese, were more likely to form pancreatic tumors than mice engineered with the KRAS mutation alone.

Muzumdars lab is now studying why beta cells switch from making insulin to Cck. Another key puzzle is how Cck can boost tumor formation and progression. Our hope is that the underlying pathways and mechanisms were identifying in obesity also may apply to those who develop pancreatic cancer in the absence of obesity, he added.

Lead authors on the paper include Jaffarguriqbal Singh and Lauren Lawres from Yale and Katherine Minjee Chung and Kimberly Judith Dorans from MITs Koch Institute of Integrative Cancer Research. Yales Cathy Garcia, Daniel Burkhardt, Rebecca Cardone, Xiaojian Zhao, Richard Kibbey, Smita Krishnaswamy and Charles Fuchs contributed to the study, as did Rebecca Robbins, Arjun Bhutkar and Tyler Jacks from MIT. Other contributors included Ana Babic, Sara Vayrynen, Andressa Dias Costa and Brian Wolpin from Dana-Farber Cancer Institute; Jonathan Nowak from Brigham and Womens Hospital; Daniel Chang of Stanford Cancer Institute; Richard Dunne and Aram Hezel of the University of Rochester Medical Center; Albert Koong of the University of Texas MD Anderson Cancer Center; Joshua Wilhelm and Melena Bellin of the University of Minnesota Medical Center; and Vibe Nylander, Anna Gloyn and Mark McCarthy of the University of Oxford.

Funding for the study was provided by the Lustgarten Foundation, the National Institutes of Health, and YCC.

About Yale Cancer Center and Smilow Cancer HospitalYale Cancer Center (YCC) is one of only 51 National Cancer Institute (NCI-designated comprehensive cancer) centers in the nation and the only such center in Connecticut. Cancer treatment for patients is available at Smilow Cancer Hospital through 13 multidisciplinary teams and at 15 Smilow Cancer Hospital Care Centers in Connecticut and Rhode Island. Smilow Cancer Hospital is accredited by the Commission on Cancer, a Quality program of the American College of Surgeons. Comprehensive cancer centers play a vital role in the advancement of the NCIs goal of reducing morbidity and mortality from cancer through scientific research, cancer prevention, and innovative cancer treatment.

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Study points to obesity as driver of pancreatic cancer - Newswise

ROSTOV-ON-DON, RUSSIA - FEBRUARY 11, 2020: Breast oncologist Yelena Chernikova examines a patient's ... [+] scan at the Rostov-on-Don Research Institute of Oncology. Valery Matytsin/TASS (Photo by Valery MatytsinTASS via Getty Images)

Researchers at Tulane University School of Medicine are celebrating a breakthrough in the fight against an aggressive breast cancer.

Theyve identified a gene that causes an aggressive form of breast cancer to rapidly grow. And most importantly, theyve found a way to flip the switch and turn the gene off to prevent cancer from occurring.

They say their studies on mice are so compelling they are seeking FDA approval to begin clinical trials.

Dr. Reza Izadpanah and his team examined the role two genes play (including one they discovered) in causing triple negative breast cancer (TNBC), which is considered the most aggressive type of breast cancer.

They specifically identified an inhibitor of the TRAF3IP2 gene, which they found suppressed the growth and spread of TNBC in mouse models that closely resemble humans.

In parallel studies, they examined how TRAF3IP2 and another gene called RAB27a play roles in the secretion of substances that can cause tumor formation.

They found that suppressing the expression of either gene led to a decline in tumor growth and spread of cancer to other organs.

When Rab27a was suppressed, the tumor didnt grow but it continued to spread a small number of cancer cells to other parts of the body. But when researchers turned off the TRAF3IP2 gene, they found no spread (metastasis) of the original tumor cells for a full year following treatment.

In addition, they say inhibiting the TRAF3IP2 gene not only stopped future tumor growth, but caused existing tumors to shrink to undetectable levels.

Dr. Izadpanah says Our findings show that both genes play a role in breast cancer growth and metastasis. This exciting discovery has revealed that TRAF3IP2 can play a role as a novel therapeutic target in breast cancer treatment.

Other researchers, such as Dr. Bysani Chandrasekar of the University of Missouri, have joined in the Tulane research efforts and found that targeting TRAF3IP2 can stop the spread of glioblastoma, a deadly brain cancer.

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Scientists Find A Switch To Turn Off A Gene That Causes Aggressive Breast Cancer - Forbes

Men with prostate cancer who were defined to have clinically low- to intermediate-risk disease according to the National Comprehensive Cancer Center (NCCN) guidelines were recategorized based on the 17-gene Oncotype DX Genomic Prostate Score, according to a study.

Overall, 62% of patients who were in the low-risk group and 34% in the intermediate-risk group were reclassified with the new genomic scoring system. This demonstrated that some patients with low-risk disease as per the NCCN guidelines may have more aggressive disease, which might require a different treatment approach.

Investigators used the 17-gene reverse transcription polymerase chain reaction (RT-PCR) prostate assay to evaluate the clinical experience of 33,000 patients with clinically low-risk prostate cancer in the United States. Investigators were able to redefine the risk assessment in these patients, which helped for better decision making and disease management.

In an interview with Targeted Oncology, Aaron E. Katz, MD, FACS, professor, Department of Urology, NYU Long Island School of Medicine, chairman, Department of Urology, Winthrop Hospital, NYU Langone Healths Perlmutter Cancer Center, discussed the findings from a study of the 17-gene Oncotype DX Genomic Prostate Score.

TARGETED ONCOLOGY: What do the NCCN guidelines state about active surveillance for patients with clinically low-risk prostate cancer?

Katz: Currently, the guidelines state that men have either very low or low risk prostate cancer, defined as a prostate-specific antigen (PSA) less than 10 and Gleason score of 6 or 7 with low risk, 3 plus 4 in tumor cores that are typically less than 5, so lets say 2 to 3 cores with less than 50% of the tumor volume and with MRI showing typically no PI-RADS 4 or 5, these are good candidates for surveillance or active surveillance based upon their life expectancy, which should be taken into consideration.

Now, understandably that many of these patients that are also in the low and even in the low to intermediate risk candidates could also be candidates for definitive therapy, whether that be radiation therapy with external beam conformal or SBRT, which is a new form of radiation that we've been using, or radical prostatectomy, which the majority of patients in this country are undergoing robotically.

To answer your question, the patients that are in the low or intermediate risk category with favorable characteristics, typically longer PSA doubling times slower PSA velocity, and normal imaging on MRI, can be considered suitable candidates for active monitoring or active surveillance. I have a program at NYU that I call active holistic surveillance where we employ dietary strategies in combination with monitoring their PSA, MRI, and a biopsy strategy, if indicated.

TARGETED ONCOLOGY:What methods currently exist for determining which patients fall under the low-risk category?

Katz: It would be the biopsy strategy, so if we have biopsies that don't show a lot of cores that don't show any indicative of a primary pattern, we do biochemical assays, like the PSA, which is very important looking at a PSA that you'd like to be under 10. Now I've personally put patients on active surveillance that have PSA higher than 10 because you also have to stratify by prostate volume. This is where MRI, I think, can be very helpful as well, not only for indicating whether or not there's a certain lesion in the prostate by PI-RADS, but also the volume of the prostate. We can come up with a strategy known as PSA density, so the lower the density, the more likely the patient would do favorably on an active surveillance program.

You also have physical examination, and I think, some institutions are getting away from doing digital rectal exams and I wonder if that's going to happen especially now that we're going to more telemedicine where we can't really examine the patient but just look at an image or look at a number like a PSA on a screen. I personally still feel that a digital rectal examination can be very helpful and making sure that there's no new change in a nodule or a hardness or a firmness, which would make me concerned that there may be disease outside the prostate and make that patient not the [ideal] candidate for active surveillance.

TARGETED ONCOLOGY:Can you provide some background on this assay in terms of its clinical validity?

Katz: The genomic assay Oncotype DX is the genomic prostate score, and the genomic prostate score has been validated by a number of institutions and as part of the NCCN guidelines now to help physicians and patients stratify as to who should or should not be on an active surveillance program. The way that it was developed was to look at a number of different genes that are expressed in the prostate, 21 genes. Some of these genes are regulated by hormones. Some of them are proliferating genes.

The nice thing about this assay is it goes through a number of different genes, number different categories of genes, and within each category, there are 2 to 4 genes within that category. The idea behind this, which is rather amazing, is that rather than looking under the microscope and seeing the cellular architecture and describing what's classically been used for many years now is the Gleason grading system. It gives us an added feature, an additional layer, by looking and isolating just the cancer cells and extracting the DNA, then doing what's called an RT-PCR reverse transcriptase polymerase chain reaction to look at the expression of specific genes that are turned on in these cells, and you can come up with a new score, a genomic prostate score, that can give us individualized specific expression within those cancer cells to determine whether or not they are more aggressive or less aggressive than what we have thought by looking at the classic Gleason grade under the microscope. So, it appears, and this is not only true for prostate but probably true for breast and colon as well, that not all of these cancers that we think are the same category act the same way.

Now we have a way of extracting the DNA and looking at the aggressiveness of the cells, and yes, it's been validated by a number of well-known neurological academic institutions, Cleveland Clinic, University of California Santa Francisco, and Johns Hopkins, as well have all done great studies validating this by looking at men that were undergoing radical prostatectomy, so they are correlating the genomic score to the final pathological grade and pathological stage of the cancer at the time of radical prostatectomy to validate it, which it was. I routinely have been using this in my patients that come to me that are considering active surveillance.

TARGETED ONCOLOGY:What is the rationale for the active surveillance study? What were the findings?

Katz: This was a study looking at the 17-gene RT-PCR assay the genomic score essay looking at the clinical experience in 33,000 patients with clinically low risk prostate cancer in the United States. What we were able to do was to redefine the risk assessment in these patients.

What we showed was that in men that were in the low and intermediate risk groups that they were recategorized based upon the new genomic score as the low risk patients who are stratified or reclassified, and thats 62%. The intermediate risk patients were re-categorized in 34%, so it's very interesting to understand that some of these patients that we consider low risk may actually a harbor some more aggressive disease and may require some definitive treatment.

We have found in our studies, and if you look at some of the studies that have been done long-term on practicing surveillance, a significant number of them will progress and will require definitive treatment. So what we're able to do now is identify these patients much earlier with this study and reclassify them as we have done so this is a clear validation of the test, this 17-gene RT PCR assay. It's an important study. I think it will change the management. It will help, as I initially started to tell you, and change the management and help both physicians and patients make a more educated decision about their treatment decision.

TARGETED ONCOLOGY:What are the key takeaways from this study?

Katz: I think the point that you want to take home is that we've relied on certain risk categories for men, based upon their Gleason, their PSA, the number of cores they have, their rectal examination. We're now moving into a new direction, into the into a new future of a new era, if you will, of molecular staging or molecular stratification. I think it's an exciting era and 1 that will continue to be expanded in its use in oncology. I think it probably will expand toward breast, ovarian, and colon cancers, as well as maybe some other cancers like leukemia or lymphoma, but it is an interesting time.

I was happy to see that we were able to do this study and look at it very carefully and critically, so I'm excited about it and am feeling encouraged that we are really a bit becauseyou have to understand that the men that come to the office, they're very anxious They've been told they have cancer. If we can find that the cancer truly is an indolent cancer, it's non-aggressive cancer that you can wait maybe 2 years, maybe 5, maybe 15 or 20 or forever in your life and don't have to undergo surgery or radiation, and I've seen that in my practice, for sure, then that's a big deal for a lot of men. Despite advances in radiation and surgery, we've made great strides with robotic surgery and stereotactic body radiotherapy, but they're not 100% curative, and they can be associated with toxicity for men, such as urinary and sexual toxicity, acutely and also chronically, so we have to be very mindful as well about the quality of life.

Reference

Bennett J, Aboushwareb T, Lau N, Stoppler M, Katz A. The 17-gene RT-PCR prostate assay: clinical experience in 33,000 patients with clinically low-risk prostate cancer. J Urol. 2020:203(suppl 4):MP23-07. doi: 10.1097/JU.0000000000000856.07

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Katz Explains the Role of Different Stratification Strategies in Prostate Cancer - Targeted Oncology

HACKENSACK, N.J. and NEW YORK, June 5, 2020 /PRNewswire/ -- As part of the Memorial Sloan Kettering Cancer Center Hackensack Meridian Health Partnership, the two organizations have formed an Immunology Research Collaboration. Through this joint initiative, researchers can apply for funding to support innovative investigations to explore the power of the immune system and ways it may be harnessed to fight cancer.

The three researchers with projects selected in 2020 for funding support over one to two years are:

"Immunotherapy has become an essential pillar of cancer treatment, but much remains to be discovered about the immune system and new ways to take advantage of its power to treat cancer effectively," said Paul Sabbatini, M.D., deputy physician-in-chief for clinical research at Memorial Sloan Kettering. "The Immunology Research Collaboration between Memorial Sloan Kettering and Hackensack Meridian Health gives researchers an opportunity to delve deeply into unexplored facets of the immune system, both in the lab and clinic, and speed discoveries that will ultimately contribute to reducing the burden of cancer on our patients, their families, and the world. We are enthusiastic about the potential of these three research projects and look forward to their results."

"While immunotherapy is revolutionizing cancer treatment, its benefits are not always sustainable over the long term," noted Andrew Goy, M.D., M.S., chairman and executive director of John Theurer Cancer Center and physician-in-chief of the Hackensack Meridian Health Oncology Care Transformation Service. "The work of these investigators will expand our knowledge of the immune system and glean new insights which may lead to novel immunotherapeutics that are more powerful and more durable than those we are using today. These projects capture the collaborative spirit of this initiative and could have a significant impact on patient outcomes."

ABOUTHACKENSACKMERIDIAN HEALTH

Hackensack Meridian Health is a leading not-for-profit health care organization that is the largest, most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care.

Hackensack Meridian Health comprises 17 hospitals from Bergen to Ocean counties, which includes three academic medical centers Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune, JFK Medical Center in Edison; two children's hospitals - Joseph M. Sanzari Children's Hospital in Hackensack, K. Hovnanian Children's Hospital in Neptune; nine community hospitals Bayshore Medical Center in Holmdel, Mountainside Medical Center in Montclair, Ocean Medical Center in Brick, Palisades Medical Center in North Bergen, Pascack Valley Medical Center in Westwood, Raritan Bay Medical Center in Old Bridge, Raritan Bay Medical Center in Perth Amboy, Riverview Medical Center in Red Bank, and Southern Ocean Medical Center in Manahawkin; a behavioral health hospital Carrier Clinic in Belle Mead; and two rehabilitation hospitals - JFK Johnson Rehabilitation Institute in Edison and Shore Rehabilitation Institute in Brick.

Additionally, the network has more than 500 patient care locations throughout the state which include ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, urgent care centers and physician practice locations. Hackensack Meridian Health has more than 35,000 team members, and 7,000 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves.

The network's notable distinctions include having four hospitals among the top in New Jersey by U.S. News and World Report. Other honors include consistently achieving Magnet recognition for nursing excellence from the American Nurses Credentialing Center and being named to Becker's Healthcare's "150 Top Places to Work in Healthcare/2019" list.

The Hackensack Meridian School of Medicine at Seton Hall University opened in 2018, the first private medical school in New Jersey in more than 50 years, welcomed its second class of 96 students in 2019 to its ON3 campus in Nutley and Clifton. Additionally, the network partnered with Memorial Sloan Kettering Cancer Center to find more cures for cancer faster while ensuring that patients have access to the highest quality, most individualized cancer care when and where they need it.

Hackensack Meridian Health is a member of AllSpire Health Partners, an interstate consortium of leading health systems, to focus on the sharing of best practices in clinical care and achieving efficiencies.

For additional information, please visit http://www.HackensackMeridianHealth.org.

ABOUT MEMORIAL SLOAN KETTERING

As the world's oldest and largest private cancer center, Memorial Sloan Kettering has devoted more than 135 years to exceptional patient care, influential educational programs, and innovative research to discover more effective strategies to prevent, control and, ultimately, cure cancer. MSK is home to more than 20,000 physicians, scientists, nurses, and staff united by a relentless dedication to conquering cancer. Today, we are one of 51 National Cancer Institute-designated Comprehensive Cancer Centers, with state-of-the-art science and technology supporting groundbreaking clinical studies, personalized treatment, and compassionate care for our patients. We also train the next generation of clinical and scientific leaders in oncology through our continually evolving educational programs, here and around the world. Year after year, we are ranked among the top two cancer hospitals in the country, consistently recognized for our expertise in adult and pediatric oncology specialties. http://www.mskcc.org.

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As a new feature on The Beet,Elysabeth Alfanointerviews notable plant-based personalities to bring you stories designed to inform and inspire you on your plant-based journey. Here, she interviewed Dr. Dean Ornish, known as the Father of Lifestyle Medicine, on howadopting a plant-based approach can boost your immune system and help you stay healthy in a time of COVID-19.

Cities around the globe are convulsing,as the need for social justice has knocked the coronavirus pandemic off the front pages. But with thevirus still marching onacross the southern United States andsmaller outbreaks are croppingup like smallforest fires in the wake ofa massive burn, it's clear the virus is not going away, no matter how much news events overtake it.

So the question is now, how can we best protect ourselves and live a healthy life, given the fact that we are as stressed as ever. Weekly Beet columnist, Elysabeth Alfano, sits down (remotely of course) with Dr. Dean Ornish, one of the foremost leaders in reversing chronic diseases, to talk about the urgency ofboosting our immune systems, now and in the months and years ahead.

Respected the world over, Dr. Ornish has proven that genes do not determine your fate. In his practice, he has shown thatdiet and exercise and stress-relieving lifestylepractices can override any predisposition to heart disease and many other chronic ailments. In fact, dietary changesspecifically a plant-based diet that is low in oilcan even reverse early or advanced stages of heart disease, diabetes, and high blood pressure.

These same lifestyle changes can also strengthen our immune systems, still the best-known defense against COVID-19, and certainly a way of avoiding the most severe symptoms if you do get infected. According toOrnish,consistently eating a whole food plant-based diet can increase your immunity and reduce the likelihood that were going to get sick, now or later in life.

In his book, UnDo It: How Simple Lifestyle Changes Can Reverse Most Diseases, written with his wife, Anne Ornish, Dr. Ornish walks us through how making some relatively small changes can, in short, reverse aging and protect us by keeping us strong. The book was recently featured by Oprah on her series, SuperSoul Sunday. She points out that it's easier to make these tweaks than to have to commit to a life of drugs, medical procedures and symptoms.

"Eat more, move more, stress less," says Oprah, summing it up, to which Dr. Ornish adds: Love more. Boom, that's it. His wife concludes: "It's really about self-love."

Its no wonder that Dr. Ornish was featured as an expert in the movie, The Game Changers. What athlete, or human, wouldnt want to age backward? However, we mere mortals arent concerned with batting 1000we just want to be able to leave our houses with a stronger immune system to protect ourselves from Coronavirus and feel as if we can live a healthy life.

Here is Dr. Ornish, on what you can do to boost your immune system now.

EA: Are your colleagues or other doctors making a connection between eating meat and the pandemic that were in right now? Or eating meat or not eating meat and having a stronger immune system?

Dr. Ornish:Well, unfortunately, most of the efforts have been on avoiding the virus rather than how we can boost our immune system to be more likely to avoid getting sick if were exposed to it. Both are important, but most of the effort has gone into the former and I think we need to put more emphasis on the latter: What we eat, how we respond to stress, how much exercise we get, how much love and support we have, how much sleep we get, and whether or not we smoke cigarettes.

Each of these are important factors that we do have control over, and I think that's important because its so easy to feel like, Oh my god, what can I do? Im a victim. Im powerless, and were not powerless.

It doesnt mean that you can go out and your immune system is so great that you dont need to worry about [the virus]. We need to avoid the virus, but it cant always be completely avoided, and so we also need to do these measures that can enhance our immune function.

Whats good for your immune system is good for your heart. Its good for diabetes. Its good for looking younger. Its good for just about most of the chronic diseases that I really think are just the same disease manifesting and masquerading in different forms, because they all share the same underlying biological mechanism. Things like, not only your immune function but chronic inflammation, oxidative stress, changes to the microbiome and telemeters and gene expression and androgenesis, and so on.

"Each one of these biological mechanisms is directly influenced, just like our immune function is, by four things:

So, its not that you only want to make these changes because of this pandemic thats out there. These are changes that are worth making because the other pandemic thats out there is heart disease and diabetes. 80 million people in this country have high blood pressure. 60 million are taking cholesterol-lowering drugs. More people die of heart disease than anything else and yet its almost completely preventable if we put into practice what we already know.

The good news is the same lifestyle changes that can help prevent or even reverse heart disease and diabetes and prostate cancer and other conditions are the same ones that could help boost our immune system, to help ward off the coronavirus as well.

EA: I love that you say this. I love that its so empowering for people. You dont have to stand in line, you dont have to go to the doctor, you dont have to hope that very expensive pills will maybe fix your situation. You can actually fix your situation right here, right now, today. That power is right on your plate and it does so many things. Its very empowering to be plant-based.

Dr. Ornish:I dont want to give people the false sense that if they eat a plant-based diet then they can go out and be exposed to the coronavirus and their immune system will protect them. That would be foolish. But no matter how hard we try to avoid the virus, invariably there are times where we may get exposed unwillingly, and how our bodies interact with that is something that we do have more control over than we once thought.

EA: What kind of work are you doing in relation to a plant-based diet and Alzheimer's disease?

Dr. Ornish:Were doing the first randomized trial to see whether these same lifestyle changes that can reverse heart disease and diabetes and prostate cancer may also reverse Alzheimers.

"I have a new book I wrote with my wife, Ann, called Undo It, which is putting forth this radical unifying theory that these are really all the same disease masquerading and manifesting in different forms because they all share the same underlying biological mechanisms (as I explained above, but are worth mentioning again). Things like chronic inflammation, oxidative stress, changes in the microbiome and telemeters, and gene expression, and each one of these mechanisms isdirectly influenced by what we eat, how we respond to stress, how much exercise we get, and how much love and support (we have).

"So, eat well, move more, stress less, and love more.Were halfway through this Alzheimers study, and Im hoping that we may be able to show that we can stop or reverse the progression of Alzheimers because there are really the same mechanisms that affect Alzheimers that affect these other conditions.

EA: And we have control over it is what youre saying, at least some of it?

Dr. Ornish: "We hope so. You know, our genes are a predisposition, but our genes are not always our fate and we did a study where we found that over 500 genes were changed in only three months (when making lifestyle changes). Turning on the good genes (with these lifestyle changes) that keep us healthy and turning off the ones that cause us to get sick. And, since there are no good drugs that are highly effective for treating Alzheimers, if we can show we can reverse it, then we can prevent it. Stay tuned, we dont know yet what well find, but were hoping that we find something that will be exciting for people.

We love you, Dr. O! Thanks for keeping us healthy, strong, and wise now and in the future. So, go forth and 1) eat plant-based, 2) reduce your stress, 3) get in that exercise and 4) get your love groove on! Cmon what could be easier? We got this!

For the full interview, click here.Elysabeth Alfano is the host of the Awesome Vegans Influencer Series, and a plant-based expert, breaking down plant-based health, food, business, and environmental news for the general public on radio and TV.

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Dean Ornish Shares 4 Tips for Healthy Immunity and Healthy Heart - The Beet

The complement system is part of the bodys immune system to fight pathogens and remove cell debris. Its role in two autoimmune diseases and a mental disorder is a surprise.

The complement system is part of the bodys immune system to fight pathogens and remove cell debris. Its role in two autoimmune diseases and a mental disorder is a surprise.Variants in a gene of the human immune system cause men and women to have different vulnerabilities to the autoimmune diseases lupus and Sjgrens syndrome, according to findings published today in the journal Nature. This extends recent work that showed the gene variants could increase risk for schizophrenia.

The gene variants are a member of the complement system, a cascade of proteins that help antibodies and phagocytic cells remove damaged cells of a persons own body, as well as an infection defense that promotes inflammation and attacks pathogens. Normally the complement system keeps a person healthy in the face of pathogens; it also helps cart away the debris of damaged human cells before the body can mount an autoimmune attack. Now complement gene variants apparently play a contributing role in the diseases systemic lupus erythematosus, Sjgrens syndrome and schizophrenia.

It had been known that all three illnesses had common genetic associations with a section of the human chromosome called the major histocompatibility complex, or MHC. This region on chromosome 6 includes many genes that regulate the immune system. However, making an association with a specific gene or with the mutational variants of a specific gene that are called alleles has been difficult, partly because the MHC on human chromosome 6 spans three million base-pairs of DNA.

The Nature paper is a collaboration of 22 authors at 10 institutions in the United States and one in England, along with many members of a schizophrenia working group. Robert Kimberly, M.D., professor of medicine at the University of Alabama at Birmingham and director of the UAB Center for Clinical and Translational Science, is a co-author of the research, which was led by corresponding author Steven McCarroll, Ph.D., assistant professor of genetics at Harvard Medical School.

The identified alleles are complement component 4A and 4B, known as C4A and C4B.

The research showed that different combinations of C4A and C4B copy numbers generate a sevenfold variation in risk for lupus and 16-fold variation in risk for Sjgrens syndrome among people with common C4 genotypes. Paradoxically, the same C4 alleles that previously were shown to increase risk for schizophrenia had a different impact for lupus and Sjgrens syndrome they greatly reduced risk in those diseases. In all three illnesses, the C4 alleles acted more strongly in men than in women.

For the complement proteins that are encoded by the genes for C4 and for complement component 3, or C3, both C4 protein and its effector C3 protein were present at greater levels in men than in women in cerebrospinal fluid and blood plasma among adults ages 20-50. Intriguingly, that is the age range when the three diseases differentially affect men and women for unknown reasons. Lupus and Sjgrens syndrome affect women of childbearing age nine times more than they do men of similar age. In contrast, in schizophrenia, women exhibit less severe symptoms, more frequent remission of symptoms, lower relapse rates and lower overall incidence than men, who are affected more frequently and more severely.

Both men and women have an age-dependent elevation of C4 and C3 protein levels in blood plasma. In men, this occurs early in adulthood, ages 20-30. In women, the elevation is closer to menopause, ages 40-50. Thus, differences in complement protein levels in men and women occur mostly during the reproductive years, ages 20-50.

The researchers say sex differences in complement protein levels may help explain the larger effects of C4 alleles in men, the greater risk of women for lupus and Sjgrens, and the greater vulnerability of men for schizophrenia.

Robert Kimberly, M.D.The ages of pronounced sex differences in complement levels correspond to the ages when men and women differ in disease incidence. In schizophrenia cases, men outnumber women in early adulthood; but that disparity of onset lessens after age 40. In lupus, female cases greatly outnumber male cases during childbearing years; but that difference is much less for disease onset after age 50 or during childhood. In Sjgrens syndrome, women are more vulnerable than are men before age 50.

The researchers say the differing effect of C4 alleles in schizophrenia versus lupus and Sjgrens syndrome will be important to consider in any therapeutic effort to engage the complement system. They also said, Why and how biology has come to create this sexual dimorphism in the complement system in humans presents interesting questions for immune and evolutionary biology.

Co-authors with McCarroll and Kimberly for the paper, Complement genes contribute sex-biased vulnerability in diverse illnesses, are Nolan Kamitaki, Aswin Sekar, Heather de Rivera, Katherine Tooley and Christine Seidman, Harvard Medical School, Massachusetts; Robert Handsaker and Christopher Whelan, Broad Institute of Massachusetts Institute of Technology; David Morris, Philip Tombleson and Timothy Vyse, Kings College London, London, United Kingdom; Kimberly Taylor and Lindsey Criswell, University of California-San Francisco School of Medicine; Loes Olde Loohuis and Roel Ophoff, University of California-Los Angeles; Michael Boehnke, University of Michigan; Kenneth Kaufman and John Harley, Cincinnati Childrens Hospital Medical Center, Ohio; Carl Langefeld, Wake Forest School of Medicine, North Carolina; Michele Pato and Carlos Pato, State University of New York, Downstate Medical Center; and Robert Graham, Genentech Inc., South San Francisco, California.

Support came from National Institutes of Health grants HG006855, MH112491, MH105641 and MH105653; and from the Stanley Center for Psychiatric Research.

At UAB, Kimberly holds the Howard L. Holley Research Chair in Rheumatology.

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Complement genes add to sex-based vulnerability in lupus and schizophrenia - UAB News