Decibel Therapeutics Announces Strategic Research Focus on Regenerative Medicine for the Inner Ear – Business Wire

BOSTON--(BUSINESS WIRE)--Decibel Therapeutics, a development-stage biotechnology company developing novel therapeutics for hearing loss and balance disorders, today announced a new strategic research focus on regenerative medicine approaches for the inner ear. The company is also announcing a collaboration and option agreement that gives Decibel exclusive access to novel compounds targeting proteins in a critical regenerative pathway.

Decibels research focus on regeneration will be powered by the companys research and translation platform. The company has built one of the most sophisticated single cell genomics and bioinformatics platforms in the industry to identify and validate targets. Decibel has also developed unique insights into regulatory pathways and inner ear delivery mechanisms that together enable precise control over gene expression in the inner ear and differentiate its AAV-based gene therapy programs.

Our deep understanding of the biology of the inner ear and our advanced technological capabilities come together to create a powerful platform for regenerative medicine therapies for hearing and balance disorders, said Laurence Reid, Ph.D., acting CEO of Decibel. We see an exciting opportunity to leverage this platform to address a broad range of hearing and balance disorders that severely compromise quality of life for hundreds of millions of people around the world.

The first program in Decibels regeneration portfolio aims to restore balance function using an AAV-based gene therapy (DB-201), which utilizes a cell-specific promoter to selectively deliver a regeneration-promoting gene to target cells. In collaboration with Regeneron Pharmaceuticals, Decibel will initially evaluate DB-201 as a treatment for bilateral vestibulopathy, a debilitating condition that significantly impairs balance, mobility, and stability of vision. Ultimately, this program may have applicability in a broad range of age-related balance disorders. There are currently no approved medicines to restore balance. Decibel expects to initiate IND-enabling experiments for this program in the first half of 2020.

Decibel is also pursuing novel targets for the regeneration of critical cells in both the vestibule and cochlea of the inner ear; these targets may be addressable by gene therapy or other therapeutic modalities. As a key component of that program, Decibel today announced an exclusive worldwide option agreement with The Rockefeller University, which has discovered a novel series of small-molecule LATS inhibitors. LATS kinases are a core component of the Hippo signaling pathway, which plays a key role in regulating both tissue regeneration and the proliferation of cells in the inner ear that are crucial to hearing and balance. The agreement gives Decibel an exclusive option to license this series of compounds across all therapeutic areas.

The agreement also establishes a research collaboration between Decibel and A. James Hudspeth, M.D., Ph.D., the F.M. Kirby Professor at The Rockefeller University and the director of the F.M. Kirby Center for Sensory Neuroscience. Dr. Hudspeth is a world-renowned neuroscientist, a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and a Howard Hughes Medical Institute investigator. Dr. Hudspeth has been the recipient of numerous prestigious awards, including the 2018 Kavli Prize in Neuroscience.

Rockefeller scientists are at the leading edge of discovery, and we are excited to see the work of Dr. Hudspeth move forward in partnership with Decibel, said Jeanne Farrell, Ph.D., associate vice president for technology advancement at The Rockefeller University. The ambitious pursuit of harnessing the power of regenerative medicine to create a new option for patients with hearing loss could transform how we address this unmet medical need in the future.

In parallel with its new research focus on regenerative strategies, Decibel will continue to advance key priority preclinical and clinical programs. DB-020, the companys clinical-stage candidate designed to prevent hearing damage in people receiving cisplatin chemotherapy, is in an ongoing Phase 1b trial. Decibel will also continue to progress DB-OTO, a gene therapy for the treatment of genetic congenital deafness, which is being developed in partnership with Regeneron Pharmaceuticals. The DB-OTO program aims to restore hearing to people born with profound hearing loss due to a mutation in the otoferlin gene and is expected to progress to clinical trials in 2021.

To support the new research focus, Decibel is restructuring its employee base and discontinuing some early-stage discovery programs.

About Decibel Therapeutics, Inc.Decibel Therapeutics, a development-stage biotechnology company, has established the worlds first comprehensive drug discovery, development, and translational research platform for hearing loss and balance disorders. Decibel is advancing a portfolio of discovery-stage programs aimed at restoring hearing and balance function to further our vision of a world in which the benefits and joys of hearing are available to all. Decibels lead therapeutic candidate, DB-020, is being investigated for the prevention of ototoxicity associated with cisplatin chemotherapy. For more information about Decibel Therapeutics, please visit decibeltx.com or follow @DecibelTx.

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Decibel Therapeutics Announces Strategic Research Focus on Regenerative Medicine for the Inner Ear - Business Wire

Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1 to | DDDT – Dove Medical Press

Ganhua You, 1, 2 Xiangshu Long, 3, 4 Fang Song, 3, 4 Jing Huang, 3, 4 Maobo Tian, 3, 4 Yan Xiao, 3, 4 Shiyan Deng, 3, 4 Qiang Wu 3, 4

1Guizhou University School of Medicine, Guiyang 550025, Peoples Republic of China; 2Guizhou Institute for Food and Drug Control, Guiyang 550004, Peoples Republic of China; 3Department of Cardiology, Guizhou Provincial Peoples Hospital, Guiyang 550002, Peoples Republic of China; 4Department of Cardiology, Peoples Hospital of Guizhou University, Guiyang 550002, Peoples Republic of China

Correspondence: Qiang WuDepartment of Cardiology, Guizhou Provincial Peoples Hospital, 83 Zhongshan East Road, Guiyang, Guizhou, Peoples Republic of ChinaTel +86-0851-85937194Fax +86-0851-85924943Email wqgz0851@126.com

Background: Metformin has been shown to inhibit the proliferation and migration of vascular wall cells. However, the mechanism through which metformin acts on atherosclerosis (AS) via the long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is still unknown. Thus, this research investigated the effect of metformin and lncRNA TUG1 on AS.Methods: First, qRT-PCR was used to detect the expression of lncRNA TUG1 in patients with coronary heart disease (CHD). Then, the correlation between metformin and TUG1 expression in vitro and their effects on proliferation, migration, and autophagy in vascular wall cells were examined. Furthermore, in vivo experiments were performed to verify the anti-AS effect of metformin and TUG1 to provide a new strategy for the prevention and treatment of AS.Results: qRT-PCR results suggested that lncRNA TUG1 expression was robustly upregulated in patients with CHD. In vitro experiments indicated that after metformin administration, the expression of lncRNA TUG1 decreased in a time-dependent manner. Metformin and TUG1 knockdown via small interfering RNA both inhibited proliferation and migration while promoted autophagy via the AMPK/mTOR pathway in vascular wall cells. In vivo experiments with a rat AS model further demonstrated that metformin and sh-TUG1 could inhibit the progression of AS.Conclusion: Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA TUG1.

Keywords: metformin, taurine up-regulated gene 1, AMPK/mTOR, autophagy, atherosclerosis

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Gene fragment could explain link between autism and cognitive difficulties: U of T study – News@UofT

Autism is associated with brilliance as well as cognitive difficulty, but how either scenario plays out in the brain is not clear. Now a study by University of Toronto researchers has found that a tiny gene fragment impacts the brain in a way that could explain swathes of autism cases that come with mental health challenges.

Researchers led byBenjamin Blencowe, a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research and Faculty of Medicine, andSabine Cordes, a senior investigator at Sinai Health Systems Lunenfeld-Tanenbaum Research Institute (LTRI), have identified a short gene segment that is crucial for brain development and information processing. Writing in the journalMolecular Cell, the researchersdescribe how an absence of this segment is sufficient to induce altered social behaviour a hallmark of autism in mice, as well as learning and memory deficits, which are seen in a subset of autism cases.

Best known for causing difficulties in social interaction and communication, autism is thought to arise from mishaps in brain wiring during development. It can strike in various ways. Those who experience it can have superior mental ability or need full-time care. Where on the autism spectrum a person falls depends in large part on their genetics, but most cases are idiopathic, or of unknown genetic origin.

Its very important to understand the mechanisms that underlie autism, especially in idiopathic forms where it is not clear what the underlying causes are, saysThomas Gonatopoulos-Pournatzis, a research associate in Blencowes lab and lead author of the study. Not only have we identified a new mechanism that contributes to this disorder, but our work may also offer a more rational development of therapeutic strategies.

Blencowes team had previously uncovered a link between autism and short gene segments, known as microexons, that are predominantly expressed in the brain. Through a process known as alternative splicing, microexons are either spliced in or left out from the final gene transcript before it is translated into a protein. Although small, microexons can have dramatic effects by impacting a proteins ability to bind its partners as required during brain development. However, how individual microexons contribute to autism is not clear.

The team focused on a specific microexon located in a gene known as eIF4G, which is critical for protein synthesis in the cell. They found that this microexon is overwhelmingly excluded from eIF4G gene transcripts in the brains of autistic individuals.

Hippocampal neurons from a normal mouse (above) and a mouse bred to lack the eIF4G microexon (below). The latter contains fewer particles that represent paused protein synthesis machineries. In these mice, higher levels of protein synthesis in neurons lead to disrupted brain waves and autistic-like behaviors as well as cognitive deficits down the line.

To test if the eIF4G microexon is important for brain function, Gonatopoulos-Pournatzis, together with Cordess team, bred mice that lack it. These mice showed social behaviour deficits, such as avoiding social interaction with other mice, establishing a link between the eIFG4 microexon and autistic-like behaviours.

A surprise came when the researchers found that these mice also performed poorly in a learning and memory test, which measures the animals ability to associate an environment with a stimulus.

We could not have imagined that a single microexon would have such an important impact not only on social behaviour but also on learning and memory, says Gonatopoulos-Pournatzis.

Further analysis revealed that the microexon encodes a part of eIF4G that allows it to associate with the Fragile X mental retardation protein, or FMRP, which is missing from people affected with Fragile X syndrome, a type of intellectual disability. About a third of individuals with Fragile X have features of autism but the link between the two remained unclear until now.

FMRPandeIF4G work together to act as a brake to hold off protein synthesis until new experience comes along, as the brake is removed by neural activity, the researchers also found.

Its important to control brain responses to experience, says Gonatopoulos-Pournatzis. This brake in protein synthesis is removed upon experience and we think it allows formation of new memories.

Without the microexon, however, this brake is weakened and what follows is increased protein production. The newly made proteins, identified in experiments performed withAnne-Claude Gingras, a senior investigator at LTRI and a professor in the department of molecular genetics, form ion channels, receptors and other signaling molecules needed to build synapses and for them to function properly.

However, making too many of these proteins is not a good thing because it leads to the disruption of the type of brain waves involved in synaptic plasticity and memory formation. This is revealed by electrode recordings of mouse brain slicesin experiments performed by the teams ofGraham Collingridge, a senior investigator at LTRI and a professor in the department of physiology, andMelanie Woodin, a professor of cell and systems biology at U of T and the dean of the Faculty of Arts & Science.

Moreover, an excess of similar kinds of proteins occurs in the absence of FMRP, suggesting a common molecular mechanism for Fragile X and idiopathic autism.

Researchers believe that their findings could help explain a substantial proportion of autism cases for which no other genetic clues are known. The findings also open the door to the development of new therapeutic approaches. One possibility is to increase the splicing of the eIF4G microexon in affected individuals using small molecules as a way to improve their social and cognitive deficits, Blencowe said.

The study would not have been possible without a close collaboration among multiple teams contributing diverse expertise. Blencowe and Gonatopoulos-Pournatzis also worked closely withJulie Forman-Kay, a professor of biochemistry and program head and senior scientist in the molecular medicine program at the Hospital for Sick Children, andNahum Sonenberg, a professor of biochemistry at McGill University.

The research was made possible by grants from the Canadian Institutes of Health Research, Simons Foundation and theCanada First Research Excellence Fund Medicine by Design program, among others.

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Here’s Why Editas Medicine Jumped 45.3% in November – The Motley Fool

What happened

Shares of Editas Medicine (NASDAQ:EDIT) rose more than 45% last month, according to data fromS&P Global Market Intelligence. The gene editing pioneer rose for reasons both internal and external.

The business announced an amended collaboration with Celgene (NASDAQ:CELG) for developing engineered immune cells and will receive an upfront payment of $70 million as a result of the new agreement. The company also enjoyed a bump from peer CRISPR Therapeutics, which reported promising results for the first two patients dosed with its lead drug candidate, CTX001. Investors took that as evidence that CRISPR-based medicines might be the real deal, although that's a mighty big leap.

The gene editing company also reported a business update and operating results for the third quarter of 2019, but there wasn't much to report for the pre-commercial entity.

Image source: Getty Images.

Editas Medicine started working with Juno Therapeutics, now owned by Celgene, in 2015. The idea was to combine the gene-editing platform of the former with the immunotherapy leadership of the latter. That's still the case, but the amended agreement scales back the specific types of engineered T cells that will be developed in the collaboration. It's a subtle, but potentially important, detail with (beneficial) ramifications for the long-term future of Editas Medicine.

It appears that the $70 million upfront payment was made in part to compensate Editas Medicine for the difference. After all, the company had already received $70 million in upfront, milestone, and execution payments under the original collaboration agreement. It's not immediately clear how the financial terms have changed, if they did at all, but the gene editing pioneer originally stood to receive up to $920 million in milestone payments.

Beyond that, there were several other updates provided in November:

The gene-editing landscape is still in the earliest stages of development. While CRISPR Therapeutics has taken an early lead as the top gene editing company, Editas Medicine is hoping to prove that its direct delivery approach will prove equally effective. The trial results the company will present in the coming years will become crucial tests for the future of CRISPR-gene editing, especially with competing techniques on the horizon.

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Here's Why Editas Medicine Jumped 45.3% in November - The Motley Fool

‘Beethoven mice’ prevent deafness: Medicine’s next big thing? – WNDU-TV

Researchers at Harvard Medical School and Boston Children's Hospital have found a potential treatment for hereditary deafness, the same condition thought to have caused Ludwig van Beethoven to lose his hearing.

The scientists are using a new gene-editing approach that they say could someday prevent profound hearing loss.

Beethoven's Symphony No. 5 is a cornerstone of classical music. It is hard to believe the composer was almost completely deaf from a genetic condition when he finished it.

"These children are born fairly normal, but then over 10 or 20 years, they lose their hearing," Harvard neurobiology professor Dr. David Corey.

Aptly named "Beethoven mice" might hold the key to a potential cure. Scientists believe the animals have a defect in the same gene that may have caused Beethoven's deafness.

"Our genome is composed of about 3 billion letters of DNA that together make up 20,000 genes," Corey explained. "For the disease we're studying, one mistake in the DNA in one of the genes causes deafness."

Researchers identified that hearing gene called TMC1. It's a gene that comes in pairs.

Using a newly refined gene-editing system, they disabled the defective copy of the TMC1 gene, leaving the good gene in place.

"By eliminating just the bad copy, that would be sufficient to preserve hearing," Corey said.

The scientists then delivered the edited DNA back into the cells of the mice and tested their hearing.

"We put little scalp electrodes on the back of the head, play sounds into the ear and can measure the brain activity in response," Boston Children's Hospital professor of otolaryngology Dr. Jeffrey Holt said.

Researchers say the mice were able to hear sounds as low as 45 decibels, the level of a quiet conversation.

"This could be life-changing," Holt said.

A famed composer, his namesake mice and a team of scientists are using cutting-edge medicine to help people who would otherwise go deaf.

The scientists say this research paves the way for using the new editing system to treat as many as 3,500 other genetic diseases that are caused by one defective copy of a gene.

It's important to note that Holt holds patents on TMC1 gene therapy.

MEDICAL BREAKTHROUGHSRESEARCH SUMMARYTOPIC: BEETHOVEN MICE PREVENT DEAFNESS: MEDICINE'S NEXT BIG THING?REPORT: MB #4689

BACKGROUND: In the United States, hearing loss affects 48 million people and can occur at birth or develop at any age. One out of three people over the age 65 have some degree of hearing loss, and two out of three people over the age 75 have a hearing loss. Children in the United States are estimated at 3 million in having a hearing loss, and of those, 1.3 million are under the age of three. One of the leading causes of hearing loss is noise, and while preventable, can be permanent. Listening to a noisy subway for just 15 minutes a day over time can cause permanent damage to one's hearing. Listening to music on a smartphone at high volumes over time can cause permanent damage to one's hearing as well. The number of people with hearing loss is more than those living with Parkinson's, epilepsy, Alzheimer's, and diabetes combined. (Source: https://chchearing.org/facts-about-hearing-loss/ and https://hearinghealthfoundation.org/hearing-loss-tinnitus-statistics/)

TREATMENTS: The treatment you receive will depend on the cause and severity of the hearing loss. A reversible cause of hearing loss is earwax blockage where your doctor may remove earwax using suction or a small tool with a loop on the end. Some types of hearing loss can be treated with surgery, including abnormalities of the ear drum or bones of hearing (ossicles). Repeated infections with persistent fluid may result in your doctor inserting small tubes to help your ears drain. If your hearing loss is due to damage to your inner ear, a hearing aid can be helpful. With more severe hearing loss and limited benefit from conventional hearing aids, a cochlear implant may be an option. Unlike a hearing aid that amplifies sound and directs it into your ear canal, a cochlear implant bypasses damaged or nonworking parts of your inner ear and directly stimulates the hearing nerve. (Source: https://www.mayoclinic.org/diseases-conditions/hearing-loss/diagnosis-treatment/drc-20373077)

GENE EDITING WITH CRISPR: Scientists at Harvard Medical School and Boston Children's Hospital have used a newly tailored gene-editing approach in mice thought to have the same genetic defect that caused famed composer Beethoven to go deaf in adulthood. CRISPR-Cas9 gene editing works by using a molecule to identify the mutant DNA sequence. Once the system pinpoints the mutated DNA, the cutting enzyme, or Cas9, "snips" it; however, the gene editors are not always accurate. Sometimes, the guide RNA that leads the enzyme to the target site and the Cas9 enzyme are not precise and could cut the wrong DNA. The Harvard and Boston Children's scientists are using a modified Cas9 enzyme derived from Staphylococcus aureus bacteria that they are finding is significantly more accurate. (Source: https://hms.harvard.edu/news/saving-beethoven)

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$125 million for Inscripta may usher in the next wave of genetic engineering – Yahoo Tech

In these waning days of the second decade of the twenty-first century, technologists and investors are beginning to lay the foundations for new, truly transformational technologies that have the potential to reshape entire industries and rewrite the rules of human understanding.

It may sound lofty, but new achievements from businesses and research institutions in areas like machine learning, quantum computing and genetic engineering mean that the futures imagined in science fiction are simply becoming science.

And among the technologies that could potentially have the biggest effect on the way we live, nothing looms larger than genetic engineering.

Investors and entrepreneurs are deploying hundreds of millions of dollars to create the tools that researchers, scientists and industry will use to re-engineer the building blocks of life to perform different functions in agriculture, manufacturing and medicine.

One of these companies, 10X Genomics, which gives users hardware and software to determine the functionality of different genetic code, has already proven how lucrative this early market can be. The company, which had its initial public offering earlier this year, is now worth $6 billion.

Another, the still-private company Inscripta, is helmed by a former 10X Genomics executive. The Boulder, Colo.-based startup is commercializing a machine that can let researchers design and manufacture small quantities of new organisms. If 10X Genomics is giving scientists and businesses a better way to read and understand the genome, then Inscripta is giving those same users a new way to write their own genetic code and make their own organisms.

It's a technology that investors are falling over themselves to finance. The company, which closed on $105 million in financing earlier in the year (through several tranches, which began in late 2018), has just raised another $125 million on the heels of launching its first commercial product. Investors in the round include new and previous investors like Paladin Capital Group, JS Capital Management, Oak HC/FT and Venrock.

"Biology has unlimited potential to positively change this world," says Kevin Ness, the chief executive of Inscripta . "It's one of the most important new technology forces that will be a major player in the global economy."

Ness sees Inscripta as breaking down one of the biggest barriers to the commercialization of genetic engineering, which is access to the technology.

While genome centers and biology foundries can manufacture massive quantities of new biological material for industrial uses, it's too costly and centralized for most researchers. "We can put the biofoundry capabilities into a box that can be pushed to a global researcher," says Ness.

Earlier this year, the company announced that it was taking orders for its first bio-manufacturing product; the new capital is designed to pay for expanding its manufacturing capabilities.

That wasn't the only barrier that Inscripta felt that it needed to break down. The company also developed a proprietary biochemistry for gene editing, hoping to avoid having to pay fees to one of the two laboratories that were engaged in a pitched legal battle over who owned the CRISPR technology (the Broad Institute and the University of California both had claims to the technology).

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$125 million for Inscripta may usher in the next wave of genetic engineering - Yahoo Tech

JAK2 gene – Genetics Home Reference – NIH

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the JAK2 gene are associated with essential thrombocythemia, a disorder characterized by an increased number of platelets, the blood cell fragments involved in normal blood clotting. The most common mutation (written as Val617Phe or V617F) replaces the protein building block (amino acid) valine with the amino acid phenylalanine at position 617 in the protein. This particular mutation is found in approximately half of people with essential thrombocythemia. A small number of affected individuals have a somatic mutation in another part of the JAK2 gene known as exon 12.

The V617F JAK2 gene mutation results in the production of a JAK2 protein that is constantly turned on (constitutively activated), which, in essential thrombocythemia, leads to the overproduction of abnormal blood cells called megakaryocytes. Because platelets are formed from megakaryocytes, the overproduction of megakaryocytes results in an increased number of platelets. Excess platelets can cause abnormal blood clotting (thrombosis), which leads to many signs and symptoms of essential thrombocythemia.

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Genetic test for anal cancer could identify those at high risk – Medical Xpress

May 25, 2017

A new test, based on a patient's epigenetics, could be an accurate and inexpensive way to find and treat those at highest risk of anal cancer - a disease with growing incidence in women, men who have sex with men (MSM) and people with HIV.

The early research by Queen Mary University of London (QMUL), which was funded by Cancer Research UK, finds that the test could lead to a reduction in painful procedures and minimise the over-treatment of people at low risk.

Anal cancer is mostly caused by human papillomavirus (HPV) - the same virus that causes cervical cancer. In 2014, the UK had around 1,300 new cases of anal cancer and 360 deaths. In addition to rising levels in women and MSM, anal cancer is more common in HIV-positive MSM with around 100 cases per 100,000, compared to 25 in HIV-negative MSM, and only 1.5 in men in general.

Diagnosis presents many challenges. Full biopsies are painful, and taking a small sample of cells ('cytology') is problematic because lesions can be hidden and clinicians give varying interpretations of results. High-resolution anoscopy, where the anal canal is examined with a high resolution magnifying instrument, is often used as the primary screening tool for high-risk populations but is uncomfortable for the patient, expensive, complex and generates subjective results.

Lead researcher Professor Attila Lorincz from QMUL said: "The widespread over-treatment of anal precancerous lesions is necessary today because we don't know which ones will progress to cancer. But this creates a large burden on anoscopy clinics in the UK and the procedures can be detrimental to people's quality of life. Many people are undergoing these procedures unnecessarily, so what we really need is precision medicine to identify those who do need treatment."

The research, published in the journal Oncotarget, involved studying anal biopsy specimens from 148 patients in London, including 116 men (mostly MSM). The specimens were analysed to look for genetic markers that may be associated with the presence of anal cancer.

The team specifically looked at the patients' epigenetics and found that all of the anal cancers showed the presence of specific epigenetic methylation markers on the patients' EPB41L3 gene (a tumour suppressor gene) and also on certain regions of their viral HPV genome.

The results suggests that epigenetic testing may be an accurate and thorough method to indicate whether a patient's lesions are destined to progress to anal cancer. This could reduce the costs, pain and anxiety from other methods of diagnosis, and minimise over-treatment of low risk people.

Professor Lorincz added: "We thought this would require a complicated genomic signature involving hundreds of genes, so we were surprised that we could get such an accurate prediction from just two biomarker genes. That's important because the expected cost of the test will be fairly low.

"Now that we can identify those at risk, and conversely, those not at risk, we hope to see a big improvement, by making sure that anoscopies and laser or chemical surgery are only given to those who need it."

Once developed, the test would involve taking a small sample of cells from the anal canal via a swab and then sending the sample off to a laboratory for epigenetic analysis.

While a test could be developed within five years, the researchers caution that the results first need to be confirmed in a much larger study across the UK, and repeated using swab samples rather than the biopsies which were used in the current study.

Dr Rachel Orritt, Cancer Research UK's health information officer, said: "This study builds on what we already know about the link between changes to cell DNA and cervical cancer, and shows that similar changes to the DNA in anal cells could suggest anal cancer.

"If other studies confirm and build upon these findings, this promising research could be used to develop a less invasive method to help doctors identify people who are at a higher risk of anal cancer and avoid unnecessary procedures for those who are at a lower risk."

The researchers say that these types of biomarker - epigenetic methylation biomarkers - are important in a large number of other diseases, and could lead to a completely new approach to diagnostics and drug therapy.

Professor Lorincz explained: "These could be the early stages of a discovery of a universal set of biomarkers for any cancer. And there may be implications on therapies, as there are new techniques where the epigenetic pathway can be targeted by drugs. This is going to be the hot new area going forward in the next 15 years, so people need to be paying attention to this space."

Explore further: Most anal lesions don't cause cancer in men, research shows

More information: 'Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions'. Attila T Lorincz, Mayura Nathan, Caroline Reuter, Rhian Warman, Mohamed A Thaha, Michael Sheaff, Natasa Vasiljevic, Amar Ahmad, Jack Cuzick, Peter Sasieni. Oncotarget, 2017.

(HealthDay) -- Anal human papillomavirus (HPV) infection and precancerous lesions are common among gay and bisexual men, but most of these cases will not progress to anal cancer, a new analysis of earlier research shows.

(HealthDay) -- Women with HIV are at increased risk for anal cancer, a new study finds.

Researchers at Women & Infants Hospital, a Care New England hospital, recently published the results of a study demonstrating a connection between anal cancer and human papillomavirus (HPV) infection.

The increase in anal cancer incidence in the U.S. between 1980 and 2005 was greatly influenced by HIV infections in males, but not females, according to a study published October 5 in the Journal of the National Cancer Institute.

(HealthDay)Anal cancer rates are on the rise in many countries. But vaccination against human papillomavirus (HPV)a virus linked to the development of anal cancermay help curb rates of the disease, a new study suggests.

A vaccine routinely used to shield against cervical cancer caused by the human papillomavirus also reduces women's risk of anal cancer, a study published by the journal The Lancet Oncology on Tuesday says.

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Sangamo Therapeutics And Pfizer Announce Collaboration For Hemophilia A Gene Therapy – PR Newswire (press release)

"With a long-standing heritage in rare disease, including hemophilia, Pfizer is an ideal partner for our Hemophilia A program," said Dr. Sandy Macrae, Sangamo's Chief Executive Officer. "We believe Pfizer's end-to-end gene therapy capabilities will enable comprehensive development and commercialization of SB-525, which could potentially benefit Hemophilia A patients around the world. This collaboration also marks an important milestone for Sangamo as we continue to make progress in the translation of our ground-breaking research into new genomic therapies to treat serious, genetically tractable diseases."

Under the terms of the collaboration agreement, Sangamo will receive a $70 million upfront payment from Pfizer. Sangamo will be responsible for conducting the SB-525 Phase 1/2 clinical study and certain manufacturing activities. Pfizer will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for SB-525 and additional products, if any. Sangamo is eligible to receive potential milestone payments of up to $475 million, including up to $300 million for the development and commercialization of SB-525 and up to $175 million for additional Hemophilia A gene therapy product candidates that may be developed under the collaboration. Sangamo will also receive tiered double-digit royalties on net sales. Additionally, Sangamo will be collaborating with Pfizer on manufacturing and technical operations utilizing viral delivery vectors.

Gene therapy is a potentially transformational technology for patients, focused on highly specialized, one-time, treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patient's cells to compensate for a defective one. The genetic material can be delivered to the cells by a variety of means, most frequently using a viral vector such as rAAV. There have been no gene therapy products approved in the U.S. to date.

Hemophilia A is a rare blood disorder caused by a genetic mutation resulting in insufficient activity of Factor VIII, a blood clotting protein the body uses to stop bleeding. There are approximately 16,000 patients in the U.S. and more than 150,000 worldwide with Hemophilia A. SB-525 is comprised of a rAAV vector carrying a Factor VIII gene construct driven by a proprietary, synthetic, liver-specific promoter. The U.S. Food and Drug Administration has cleared initiation of human clinical trials for SB-525, which also has been granted orphan drug designation. Sangamo is on track this quarter to start a Phase 1/2 clinical trial to evaluate safety and to measure blood levels of Factor VIII protein and other efficacy endpoints.

Conference CallSangamo will host a conference call today, May 10, 2017 at 5:00 p.m. ET, which will be open to the public, to discuss the details of the collaboration and the Company's first quarter business and financial results. The call will also be webcast live and can be accessed via a link the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A replay of the webcast will also be available for one week after the call.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 15225000. For those unable to listen in at the designated time, a conference call replay will be available for one week following the conference call, from approximately 8:00 p.m. ET on May 10, 2017 to 11:59 p.m. ET on May 17, 2017. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 15225000.

About Sangamo Therapeutics Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic therapies that transform patients' lives using the company's industry leading platform technologies in genome editing, gene therapy, gene regulation and cell therapy. The Company is advancing Phase 1/2 clinical programs in Hemophilia A and Hemophilia B, and lysosomal storage disorders MPS I and MPS II. Sangamo has a strategic collaboration with Pfizer for Hemophilia A, with Bioverativ Inc. for hemoglobinopathies, including beta thalassemia and sickle cell disease, and with Shire International GmbH to develop therapeutics for Huntington's disease. In addition, it has established strategic partnerships with companies in non-therapeutic applications of its technology, including Sigma-Aldrich Corporation and Dow AgroSciences. For more information about Sangamo, visit the Company's website at http://www.sangamo.com.

Forward Looking Statements This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation references relating to the collaboration agreement with Pfizer, potential milestone payments and royalties under the collaboration agreement, ability of the collaboration to advance and commercialize SB-525 as a treatment for Hemophilia A, research and development of therapeutic applications of Sangamo's genomic therapy platforms, the expected timing of clinical trials of lead programs, including SB-525 and the release of data from these trials, the impact of Sangamo's clinical trials on the field of genetic medicine and the benefit of orphan drug status. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to substantial dependence on the clinical success of lead therapeutic programs, the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's SEC filings, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo Therapeutics, Inc. assumes no obligation to update the forward-looking information contained in this press release.

Pfizer and Rare DiseaseRare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide,i representing an opportunity to apply our knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare disease builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within a number of disease areas of focus, including hematology, neuroscience, and inherited metabolic disorders.ii

Pfizer Rare Disease combines pioneering science and deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. We innovate every day leveraging our global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about our Rare Disease portfolio and how we empower patients, engage communities in our clinical development programs, and support programs that heighten disease awareness and meet the needs of patient families.

Pfizer Inc: Working together for a healthier worldAt Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. For more information, please visit us at http://www.pfizer.com. In addition, to learn more, follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Pfizer Disclosure Notice: The information contained in this release is as of May 10, 2017. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about an investigational Hemophilia A agent, SB-525, including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical study commencement and completion dates as well as the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing clinical data; risks associated with initial data, including the risk that the final results of the Phase I/2 study for SB-525 and/or additional clinical trials may be different from (including less favorable than) the initial data results and may not support further clinical development; whether and when any applications may be filed with regulatory authorities for SB-525; whether and when regulatory authorities may approve any such applications, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of SB-525; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2016 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at http://www.sec.gov and http://www.pfizer.com.

i Rare Disease: Facts and Statistics. http://globalgenes.org/rare-diseases-facts-statistics. Accessed September 7, 2016. ii Pfizer Inc. Rare Disease. http://www.pfizer.com/health-and-wellness/health-topics/rare-diseases/areas-of-focus. Accessed December 20, 2016.

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Type 1 diabetes cured in mice using gene therapy – Medical News … – Medical News Today

Researchers from the University of Texas Health Science Center in San Antonio have found a way to cure type 1 diabetes in mice. It is hoped that the novel technique - which boosts insulin secretion in the pancreas - will reach human clinical trials in the next 3 years.

Study co-author Dr. Bruno Doiron, Ph.D., of the Division of Diabetes, and colleagues recently reported their findings in the journal Current Pharmaceutical Biotechnology.

Type 1 diabetes is estimated to affect around 1.25 million children and adults in the United States. Onset of the condition is most common in childhood, but it can arise at any age.

In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas. Insulin is the hormone that regulates blood glucose levels. As a result, blood glucose levels become too high.

There is currently no cure for type 1 diabetes; the condition is managed through diet and insulin therapy. However, in recent years, researchers have investigated replacing beta cells as a means of eradicating type 1 diabetes once and for all.

Dr. Doiron and colleagues have taken a different approach with their new study. The team reveals how they used a method called gene transfer to coax other pancreatic cells into producing insulin.

Using this technique, the researchers have managed to cure type 1 diabetes in mice, bringing us one step closer to curing the condition in humans.

The gene transfer technique - called Cellular Networking, Integration and Processing - involves introducing specific genes into the pancreas using a virus as a vector.

The team notes that beta cells are rejected in patients with type 1 diabetes. With the gene transfer method, the newly introduced genes encourage non-beta cells to produce insulin, without any side effects.

"The pancreas has many other cell types besides beta cells, and our approach is to alter these cells so that they start to secrete insulin, but only in response to glucose [sugar]," says study co-author Dr. Ralph DeFronzo, chief of the Division of Diabetes. "This is basically just like beta cells."

Upon testing their technique on mouse models of type 1 diabetes, the researchers found that they were able to induce long-term insulin secretion and blood glucose regulation, with no adverse side effects.

"It worked perfectly. We cured mice for 1 year without any side effects. That's never been seen. But it's a mouse model, so caution is needed. We want to bring this to large animals that are closer to humans in physiology of the endocrine system."

Dr. Bruno Doiron, Ph.D.

Importantly, the researchers point out that the gene transfer therapy only releases insulin in response to blood sugar, so it has the potential to transform current treatments for type 1 diabetes.

"A major problem we have in the field of type 1 diabetes is hypoglycemia (low blood sugar)," says Dr. Doiron. "The gene transfer we propose is remarkable because the altered cells match the characteristics of beta cells. Insulin is only released in response to glucose."

Not only could the novel strategy yield a cure for type 1 diabetes, but the researchers say that it may also eliminate the need for insulin therapy in patients with type 2 diabetes, which arises when the body is unable to use insulin effectively.

It will cost around $5 million to test their technique in large animal models, but the researchers are confident that this can be achieved. They hope to reach human clinical trials within the next 3 years.

Learn how maternal omega-3 intake may influence the risk of type 1 diabetes in infants.

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All women should get tested for cancer gene, says scientist who led discovery – Champaign/Urbana News-Gazette

URBANA The scientist who led the discovery of genes responsible for 15 percent of all breast cancers says every woman age 30 and over should be tested for those genetic mutations, regardless of family history.

And women with a family history of reproductive cancer not linked to the BRCA1 or BRCA2 genes should get more extensive genetic testing, says Mary-Claire King, professor of genome sciences and medicine at the University of Washington School of Medicine.

King spoke at the University of Illinois on Monday afternoon at a talk marking the 10th anniversary of the Institute of Genomic Biology.

King said genetic testing is important for cancer prevention and treatment and for families themselves, and should be part of every woman's complete medical care. More than 40,000 women die of breast cancer, and 14,000 from ovarian cancer, each year.

"It's technically easy to do. It's not expensive to do," King said. "The major cost is not the testing itself. The major cost is how to care for women who turn out to have mutations, because they have to be cared for."

But preventive surgery is much less expensive than caring for a cancer patient, she said.

King and her colleagues spent 17 years finding and mapping the BRCA1 gene, which can cause both breast and ovarian cancer. In 1994, the gene was successfully cloned, and the closely related BRCA2 gene was cloned the following year. The discovery revolutionized genetics and cancer treatment.

Mutations in the gene interfere with the repair of DNA, deoxyribonucleic acid, the hereditary material in every human cell.

Women, or men, who carry the mutation have a higher risk of developing cancer. One study showed 80 percent of women with the mutation developed breast or ovarian cancer by age 80. In some families, there's also an increased risk of pancreatic or prostate cancer with the genetic mutations, though not as large, she said.

The mutation can be inherited through a father, not just a mother. One big challenge is getting physicians to ask patients about a history of breast or ovarian cancer in their father's family, not just their mother's, King said.

Because families are smaller than in the past, a history of breast or ovarian cancer might not be as obvious as it was in the 19th or early 20th centuries, when multiple family members may have gotten the disease, she said.

"In about 50 percent of the women in whom we identify inherited mutations of these genes, there's no immediate family history of breast or ovarian cancer that would have triggered concern," she said.

Before the work of King and other geneticists, scientists had different theories about the causes of breast cancer, from diet and stress to the use of contraceptives to a possible genetic link.

King started by identifying hundreds of families with long histories of breast and ovarian cancer.

She was able to show linkages across multiple generations and eventually narrowed the gene to a specific chromosome, then went on to isolate the gene in the lab.

There are more than 1,000 different mutations within the BRCA1 and BRCA2 genes, and more left to discover, she said.

King and her colleagues have now studied more than 5,000 families, including some "mystery families" where no common genetic mutation has been found. Researchers are sequencing the entire genome for women in those families, she said.

The cost of genetic sequencing has dropped precipitously since the Supreme Court ruled in 2013 that human genes cannot be patented, she said. The cost, around $250, is well within the budget of middle-class women, but "DNA repair does not care if you are middle class or not," she said.

It should be considered a public health issue, similar to vaccinations for contagious diseases, so every women has access to screening, she said.

The disease is an important public health problem, the risk of disease due to genetic mutation is high, the mutations responsible for the disease can be accurately identified, and effective treatments exist for women identified at risk, she said.

"They are not pretty, but they exist, and they work," she said.

Preventive surgery, such as a mastectomy or the removal of the ovaries and fallopian tubes between the ages of 35 and 40, has proven to drastically reduce cancer risk, she said.

And the study of how the BRCA1 and BRCA2 genes work has led to chemotherapy treatments that effectively target the tumors, she said.

Studies of women with the genetic mutation show that those born more recently have a higher risk of developing breast cancer, even if it's the same mutation in the same family, King said.

"This difference cannot be genetics. The difference must be changes in lifestyle," she said.

Research has shown that the earlier a girl starts her period, and the later she has her first child, her cancer risk increases. At the start of the 20th century, the average girl started menstruating at age 16 and had her first child by age 21. Today, the average start is about age 11, and more women are postponing childbirth until after age 30, King said.

Other than the genetic mutations, much of the increase in breast cancer worldwide can be pinned on those factors, she said.

UI Professor Gene Robinson, director of the Institute for Genomic Biology, said King's work has "changed the way we think of the role of genes in diseases that have both genetic and environmental causes," and how genetic therapy can help cancer patients make decisions about their health.

King has also used genetic science for humanitarian causes, to identify victims of human rights abuses in Rwanda, Serbia, the Philippines and South America, he said.

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Dermatology – Stanford University School of Medicine …

Researchers named Outstanding Investigators by the National Cancer Institute-Howard Chang, Professor of Dermatology isfeaturedthis article...Full Article

How to reduce wrinkles without lasers or chemicals - S. Tyler Hollmig, Clinical Assistant professor of Dermatology is featured in this article...Full Article

Stanford team is growing healthy skin for ill patients-Jean Tang, Associate Professor of Dermatology;Peter Marinkovich, Associate Professor of Dermatology; andAnthony Oro, Professor of Dermatology are quoted in this article...Full Article

KGO TV- Filmmakers Tap Quarterback Legend To Fight Skin Cancer - Susan Swetter, MD, Stanford Professor of Dermatology isfeatured in this article...Full Article

Automated dermatologist' detects skin cancer with expert accuracy- Roberto Novoa, Clinical Assistant Professor is featured in this article...Full Article

Deep learning algorithm does as well as dermatologists in identifying skin cancer- Susan Swetter, MD, Justin Ko, MD MBA, Roberto Novoa, MD are featured in this article...Full Article

Gene therapy for blistering skin disease appears to enhance healing in clinical trial- Peter Marinkovich, MD, andJean Tang, MD, PhD, Associate Professors of Dermatologyare featured in this articleFull Article

Factors to consider before genetic testing -Joyce Teng, Clinical Associate Professor of Dermatology is featured in this articleFull Article

USPSTF: Not enough proof for visual skin Ca screening- Susan Swetter, MD, Stanford Professor of Dermatology is quoted in this article...Full Article

Possible psoriasis drug target identified - Peter Marinkovich, MD, Stanford Associate Professor of Dermatology is featured in this articleFull Story

5 Questions: Susan Swetter on choosing a sunscreen-Susan Swetter, MD, Stanford Professorof Dermatology is featured in this article....Full Article

Acne treatments: A Q&A with Stanford dermatologist Justin Ko-Justin Ko, MD, MBA, Stanford clinical assistant professor of Dermatology is featured in this article....Full Article

Ultraviolet light-induced Mutation Drives Many Skin Cancers-Paul Khavari, MD, PhD, Carl J Herzog Professor of Dermatology and chair of the Department of Dermatology is quoted on this study...Full Story

Disproportionate Rates of Melanoma Found in Marin County-Stanford professor of Dermatology, Susan Swetter, MD,, is featured in this audio forum...Audio

Antifungal drug may treat common skin cancer, study finds-Stanford associate professor of Dermatology, Jean Tang, MD, PhD, is featured in this article...Full Story

Inflammatory skin damage in mice blocked by bleach solution, study finds...Thomas Leung, MD, PhD, Stanford instructor of Dermatology and lead author comments....Full Story

New study: Genes may affect skin youthfulness...Anne Lynn S Chang, MD, Stanford assistant professor of Dermatology comments....SCOPE Blog

Melanoma deaths more likely in young men than women...Susan Swetter, MD., professor of Dermatology at Stanford is quoted....Full Story

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How to weather summer's health challenges...Playing it safe in the sun...Susan Swetter, MD and Brooks Bahr, MD., Stanford Dermatologists are featured....See Newsletter

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Ambry Genetics Recruits Patient Cohorts to Discover New Links between Genes and Autism – Yahoo Finance

ALISO VIEJO, Calif.--(BUSINESS WIRE)--

Ambry Genetics Corporation (Ambry) is calling on psychiatrists, psychologists and behavioral specialists to encourage their patients with autism, along with their family members, to sign up for a new study conducted through Ambrys data sharing program, AmbryShare. With this program, Ambry is taking a step towards discovering possible associations between genes and autism, so clinicians can provide their patients with targeted treatments and therapies much earlier in life.

Whats unique about AmbryShares approach is that we collect genetic information from clinics and families from all over the world to answer questions that cant be answered with just a handful of patients, said Brigette Tippin Davis, PhD, Ambrys Director of Emerging Genetic Medicine. The great thing about Ambry partnerships is that we are building connections between research institutions and empowering them to develop new approaches to treating patients with autism based on genetic profiles.

So far, dozens of behavioral clinics and other medical offices have contributed to AmbryShare studies by encouraging participation from their patients. Ambry strives to enroll more than 10,000 patients from clinics nationally and internationally.

Genetic testing would allow us to personalize treatment from a genetic profile and optimize it together with our rich behavioral data, said Dennis Dixon, PhD, Chief Strategy Officer at Center for Autism and Related Disorders (CARD). I really value working with Ambry, knowing this data will have an impact on treatment for our patients and then will still be available for other researchers to access to answer additional research questions. As we each put more samples in, it increases the overall likelihood that were going to find something that really makes a difference.

One in 64 children in the United States is diagnosed with an autism spectrum disorder (ASD), which can impact social interaction, communication and behavior. Genetic testing can help identify an underlying cause in up to 40% of autism spectrum disorders. Some genetic causes include chromosome microdeletions/microduplications, fragile X syndrome, Angelman syndrome, and tuberous sclerosis. New gene discovery can allow clinicians to determine their patients course of treatment and the gene-disease relationship associated with their individual case of autism. Through the recruitment of a massive cohort, more data will be collected to discover more genes, develop medical management plans and enact preventive strategies.

The scientists need the data to be out there, said Charles Dunlop, Ambrys President and Chairman. We need to know what these diseases are actually doing, what causes them, what gene mutations are associated with them so we can move forward as an industry and move onto the next phase where there is no disease of any kind. A phase where pharmaceutical researchers know exactly what to do, or exactly what problems theyre trying to solve at a minutiae levelthats when the cures come.

In 2016, Mayo Clinic and University of Utah collaborated with Ambry on a new research study of more than 60,000 patients to help refine breast cancer risk estimates from predisposition genes that are either previously lacking data or have limited data. The study, Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients represented the largest genetic study of women with hereditary breast cancer. The large amount of data was able to provide researchers with new information about genes that contributed to breast cancer risk. Ambry wants to provide researchers with the same capabilities for autism.

Since 2001, Ambry has been dedicated to scientific research to help empower the scientific community and refine clinician management guidelines so patients may receive tailored medical management. AmbryShares initial launch in 2016 provided scientific researchers and clinicians with the largest open, de-identified database of hereditary breast and ovarian cancer cohorts with the goal of achieving a greater understanding of human disease.

For more information and to enroll in the AmbryShare autism study, visit the AmbryShare portal here.

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ABOUT AMBRY GENETICS

Ambry Genetics is both College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified. Ambry leads in clinical genetic diagnostics and genetics software solutions, combining both to offer the most comprehensive testing menu in the industry. Ambry has established a reputation for sharing data while safeguarding patient privacy, unparalleled service, and responsibly applying new technologies to the clinical molecular diagnostics market. For more information about Ambry Genetics, visit http://www.ambrygen.com.

About the Center for Autism and Related Disorders (CARD)

CARD treats individuals of all ages who are diagnosed with autism spectrum disorder (ASD) at treatment centers around the globe. CARD was founded in 1990 by leading autism expert and clinical psychologist Doreen Granpeesheh, PhD, BCBA-D. CARD treats individuals with ASD using the principles of applied behavior analysis (ABA), which is empirically proven to be the most effective method for treating individuals with ASD and recommended by the American Academy of Pediatrics and the US Surgeon General. CARD employs a dedicated team of over 3,000 individuals across the nation and internationally.

For more information, visit http://www.centerforautism.com or call (855) 345-2273.

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Ambry Genetics Recruits Patient Cohorts to Discover New Links between Genes and Autism - Yahoo Finance

Redpin Launches with $15.5 Million Series A to Focus on Pain and Epilepsy – BioSpace

Redpin Therapeutics closed on a $15.5 million Series A financing round. The round was led by 4BIO Capital and Arkin Bio Ventures. They were joined by new investor Takeda Venture Investments, as well as existing seed-round investors, New York Ventures and Alexandria Venture Investments.

Based in New York City, Redpin has a proprietary chemogenetics platform for targeted cell therapies. Its a mix of synthetic biology, gene therapy and traditional pharmacotherapy. The focus is built on an ultrapotent ion channel-based chemogenetics platform that allows targeted cell activation or inhibition controlled by low doses of the Pfizers anti-smoking drug varenicline (Chantix). The company has a worldwide exclusive license from the Howard Hughes Medical Institute for therapeutic use of the technology.

The funds will let Redpin continue to progress its platform to disorders with neural circuit dysfunction, including epilepsy, neuropathic pain and Parkinsons disease. Treatment for these usually uses systemic drugs that target local neuron dysfunction. This has the downside of adverse, off-target side effects. The lead programs are for epilepsy and chronic pain.

Redpins approach, the company believes, will be more targeted on the dysfunctional neurons while not affecting normal functioning cells. The company indicates its approach will only be activated in the presence of Chantix.

These new funds combined with the support and expertise of our new and existing investors will allow Redpin to swiftly progress to the next phase of its development in bringing highly targeted treatments to patients with neurological and psychiatric disorders, said Elma Hawkins, co-founder, president and chief executive officer of Redpin.

Chantix attaches to proteins called ion channels, which control neuron signaling. By controlling which neurons receive these proteins, researchers can modulate specific cells. In March 2019, Scott Sternson, group leader at the Howard Hughes Medical Institutes Janelia Research Campus, noted that chemogenetics often use molecules that would not be appropriate for human therapy. Its still many steps to the clinic, but were trying to shorten that route.

Sternson is one of the companys founders, along with Hawkins, Jeffrey M. Friedman at Howard Hughes, Michael Kaplitt, with Weill Cornell Medicine, Sarah Stanley at Icahn School of Medicine Mount Sinai, and Jonathan S. Dordick, Rensselaer Polytechnic Institute.

At that time, Sternson and his team modified the structure of two different ion channel proteins so the drug would be more likely to bind. One protein stimulates neurons to send messages when Chantix attaches. Another protein blocks neurons from sending those messages when Chantix is present. At that time, doses of Chantix much lower than required to quit smoking were found to have a large effect on neural activity.

Redpins technology uses adeno-associated virus (AAV) vectors to transport engineered ion channels to targeted cells. Once activated, they can control the function of the particular cell. Chantix was chosen because it is approved in 80 countries, has the necessary pharmacokinetic properties, and can penetrate the blood-brain barrier. The company has other small molecule-receptor pairs in its pipeline.

Chantix basically acts as a switch to turn the ion channel on and off.

Dmitry Kuzmin, managing partner at 4BIO, said, Our goal is to support and grow advanced therapy companies with the potential to cure chronic disease. Redpin has a highly compelling, validated chemogenetics approach that could have significant potential in the targeted treatment of neuropathic disorders. The strength of Redpins science alongside the world-class knowledge and expertise of the Companys founders and management team make us fully confident in the future success of the Company towards this goal.

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AskBio Enters Research Collaboration and Licensing Agreement with University of North Carolina (UNC) for Angelman Syndrome – Associated Press

RESEARCH TRIANGLE PARK, N.C. and CHAPEL HILL, N.C., March 18, 2020 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical, Inc. (AskBio), a leading clinical-stage adeno-associated virus (AAV) gene therapy company, today announced that it has entered into a research collaboration and licensing agreement with the University of North Carolina at Chapel Hill (UNC) for the development and commercialization of gene therapy for Angelman syndrome.

This collaboration allows us to leverage groundbreaking research from UNC and apply our AAV development capabilities to find a gene therapy treatment for Angelman syndrome, said Sheila Mikhail, JD, MBA, AskBio Chief Executive Officer and co-founder. We look forward to advancing this program together.

Angelman syndrome is a rare neurogenetic disorder caused by the loss of function of the UBE3A gene. The disorder occurs in approximately one in 15,000 people, or about 500,000 individuals worldwide, and there is currently no cure. In addition to life-altering symptoms such as speech and motor deficits, more than 80 percent of Angelman syndrome patients experience epilepsy, which typically does not respond well to standard anti-seizure medications.

A UNC School of Medicine team, led by Mark Zylka, PhD, and Ben Philpot, PhD, has generated preclinical evidence that gene therapy may help individuals with Angelman syndrome by improving seizure and motor outcomes.

Individuals with Angelman syndrome face lifelong challenges, and our gene therapy approaches hold the potential to correct this disorder at its genetic roots. We are incredibly excited to partner with AskBio, as they have been vanguards of clinical gene therapies for rare diseases, said Mark Zylka, PhD, Director of the UNC Neuroscience Center. Ben Philpot, PhD, Associate Director of the UNC Neuroscience Center added, We look forward to advancing this transformative treatment to the clinic and potentially improving the lives of individuals with Angelman syndrome.

The partnership between AskBio and UNC could transform the lives of people living with Angelman syndrome by providing them with a potential therapy for this rare disease, said Amanda Moore, Angelman Syndrome Foundation CEO. The Angelman Syndrome Foundation has long been proud to support the work of UNC researchers, Drs. Ben Philpot and Mark Zylka, and invest in science that positively affects the Angelman syndrome community. The collaboration between UNC and AskBio brings us a step closer to delivering a viable gene therapy to the people and families we serve.

The financial terms of the agreement were not disclosed.

More about Angelman SyndromeDeletion of the maternally inherited copy of the UBE3A gene causes Angelman syndrome. Symptoms include microcephaly (small head circumference), severe intellectual disability, seizures, balance and movement problems (ataxia), lack of speech, and sleep problems. Behavioral symptoms include frequent laughing, smiling and excitability. Angelman syndrome was first described in 1965, yet no treatment options have been approved in the 55 years since. While individuals with the disorder have a normal lifespan, they require life-long care and are not able to live independently.

About Angelman Syndrome FoundationThe mission of the Angelman Syndrome Foundation is to advance the awareness and treatment of Angelman syndrome through education and information, research and support for individuals with Angelman syndrome, their families and other concerned parties. We exist to give them a reason to smile, with the ultimate goal of finding a cure. To learn more, visit https://www.angelman.org.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive adeno-associated virus (AAV) capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more at https://www.askbio.com or follow us on LinkedIn.

Media Contacts: AskBio Robin Fastenau Vice President, Communications +1 984.275.2705 rfastenau@askbio.com Angelman Syndrome Foundation Amanda Moore Chief Executive Officer +1 317.514.6918 amoore@angelman.org UNC Health | UNC School of Medicine Mark Derewicz Director, Research & News +1 984.974.1915 Mark.Derewicz@unchealth.unc.edu

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AskBio Enters Research Collaboration and Licensing Agreement with University of North Carolina (UNC) for Angelman Syndrome - Associated Press

10 Breakthrough Technologies 2020 – MIT Technology Review

Here is our annual list of technological advances that we believe will make a real difference in solving important problems. How do we pick? We avoid the one-off tricks, the overhyped new gadgets. Instead we look for those breakthroughs that will truly change how we live and work.

This story is part of our March/April 2020 Issue

Were excited to announce that with this years list were also launching our very first editorial podcast, Deep Tech, which will explore the the people, places, and ideas featured in our most ambitious journalism. Have a listen here.

Later this year, Dutch researchers will complete a quantum internet between Delft and the Hague.

Yoshi Sodeoka

An internet based on quantum physics will soon enable inherently secure communication. A team led by Stephanie Wehner, at Delft University of Technology, is building a network connecting four cities in the Netherlands entirely by means of quantum technology. Messages sent over this network will be unhackable.

In the last few years, scientists have learned to transmit pairs of photons across fiber-optic cables in a way that absolutely protects the information encoded in them. A team in China used a form of the technology to construct a 2,000-kilometer network backbone between Beijing and Shanghaibut that project relies partly on classical components that periodically break the quantum link before establishing a new one, introducing the risk of hacking.

The Delft network, in contrast, will be the first to transmit information between cities using quantum techniques from end to end.

The technology relies on a quantum behavior of atomic particles called entanglement. Entangled photons cant be covertly read without disrupting their content.

But entangled particles are difficult to create, and harder still to transmit over long distances. Wehners team has demonstrated it can send them more than 1.5 kilometers (0.93 miles), and they are confident they can set up a quantum link between Delft and the Hague by around the end of this year. Ensuring an unbroken connection over greater distances will require quantum repeaters that extend the network.

Such repeaters are currently in design at Delft and elsewhere. The first should be completed in the next five to six years, says Wehner, with a global quantum network following by the end of the decade.

Russ Juskalian

Novel drugs are being designed to treatunique genetic mutations.

Julia Dufoss

Heres a definition of a hopeless case: a child with a fatal disease so exceedingly rare that not only is there no treatment, theres not even anyone in a lab coat studying it. Too rare to care, goes the saying.

Thats about to change, thanks to new classes of drugs that can be tailored to a persons genes. If an extremely rare disease is caused by a specific DNA mistakeas several thousand aretheres now at least a fighting chance for a genetic fix.

One such case is that of Mila Makovec, a little girl suffering from a devastating illness caused by a unique genetic mutation, who got a drug manufactured just for her. Her case made the New England Journal of Medicine in October, after doctors moved from a readout of her genetic error to a treatment in just a year. They called the drug milasen, after her.

The treatment hasnt cured Mila. But it seems to have stabilized her condition: it has reduced her seizures, and she has begun to stand and walk with assistance.

Milas treatment was possible because creating a gene medicine has never been faster or had a better chance of working. The new medicines might take the form of gene replacement, gene editing, or antisense (the type Mila received), a sort of molecular eraser, which erases or fixes erroneous genetic messages. What the treatments have in common is that they can be programmed, in digital fashion and with digital speed, to correct or compensate for inherited diseases, letter for DNA letter.

How many stories like Milas are there? So far, just a handful.

But more are on the way. Where researchers would have once seen obstacles and said Im sorry, they now see solutions in DNA and think maybe they can help.

The real challenge for n-of-1 treatments (a reference to the number of people who get the drug) is that they defy just about every accepted notion of how pharmaceuticals should be developed, tested, and sold. Who will pay for these drugs when they help one person, but still take large teams to design and manufacture?

Antonio Regalado

The rise of digitalcurrency has massive ramifications forfinancial privacy.

Last June Facebook unveiled a global digital currency called Libra. The idea triggered a backlash and Libra may never launch, at least not in the way it was originally envisioned. But its still made a difference: just days after Facebooks announcement, an official from the Peoples Bank of China implied that it would speed the development of its own digital currency in response. Now China is poised to become the first major economy to issue a digital version of its money, which it intends as a replacement for physical cash.

Chinas leaders apparently see Libra, meant to be backed by a reserve that will be mostly US dollars, as a threat: it could reinforce Americas disproportionate power over the global financial system, which stems from the dollars role as the worlds de facto reserve currency. Some suspect China intends to promote its digital renminbi internationally.

Now Facebooks Libra pitch has become geopolitical. In October, CEO Mark Zuckerberg promised Congress that Libra will extend Americas financial leadership as well as our democratic values and oversight around the world. The digital money wars have begun.

Mike Orcutt

Drugs that try to treat ailments bytargeting a natural aging process in the body have shown promise.

Yoshi Sodeoka

The first wave of a new class of anti-aging drugs have begun human testing. These drugs wont let you live longer (yet) but aim to treat specific ailments by slowing or reversing a fundamental process of aging.

The drugs are called senolyticsthey work by removing certain cells that accumulate as we age. Known as senescent cells, they can create low-level inflammation that suppresses normal mechanisms of cellular repair and creates a toxic environment for neighboring cells.

In June, San Franciscobased Unity Biotechnology reported initial results in patients with mild to severe osteoarthritis of the knee. Results from a larger clinical trial are expected in the second half of 2020. The company is also developing similar drugs to treat age-related diseases of the eyes and lungs, among other conditions.

Senolytics are now in human tests, along with a number of other promising approaches targeting the biological processes that lie at the root of aging and various diseases.

A company called Alkahest injects patients with components found in young peoples blood and says it hopes to halt cognitive and functional decline in patients suffering from mild to moderate Alzheimers disease. The company also has drugs for Parkinsons and dementia in human testing.

And in December, researchers at Drexel University College of Medicine even tried to see if a cream including the immune-suppressing drug rapamycin could slow aging in human skin.

The tests reflect researchers expanding efforts to learn if the many diseases associated with getting oldersuch as heart diseases, arthritis, cancer, and dementiacan be hacked to delay their onset.

Adam Piore

Scientists have used AI to discover promising drug-like compounds.

The universe of molecules that could be turned into potentially life-saving drugs is mind-boggling in size: researchers estimate the number at around 1060. Thats more than all the atoms in the solar system, offering virtually unlimited chemical possibilitiesif only chemists could find the worthwhile ones.

Now machine-learning tools can explore large databases of existing molecules and their properties, using the information to generate new possibilities. This could make it faster and cheaper to discover new drug candidates.

In September, a team of researchers at Hong Kongbased Insilico Medicine and the University of Toronto took a convincing step toward showing that the strategy works by synthesizing several drug candidates found by AI algorithms.

Using techniques like deep learning and generative models similar to the ones that allowed a computer to beat the world champion at the ancient game of Go, the researchers identified some 30,000 novel molecules with desirable properties. They selected six to synthesize and test. One was particularly active and proved promising in animal tests.

Chemists in drug discovery often dream up new moleculesan art honed by years of experience and, among the best drug hunters, by a keen intuition. Now these scientists have a new tool to expand their imaginations.

David Rotman

We can now affordably build, launch, and operate tens of thousands of satellites in orbit at once.

Julia Dufoss

Satellites that can beam a broadband connection to internet terminals. As long as these terminals have a clear view of the sky, they can deliver internet to any nearby devices. SpaceX alone wants to send more than 4.5 times more satellites into orbit this decade than humans have ever launched since Sputnik.

These mega-constellations are feasible because we have learned how to build smaller satellites and launch them more cheaply. During the space shuttle era, launching a satellite into space cost roughly $24,800 per pound. A small communications satellite that weighed four tons cost nearly $200 million to fly up.

Today a SpaceX Starlink satellite weighs about 500 pounds (227 kilograms). Reusable architecture and cheaper manufacturing mean we can strap dozens of them onto rockets to greatly lower the cost; a SpaceX Falcon 9 launch today costs about $1,240 per pound.

The first 120 Starlink satellites went up last year, and the company planned to launch batches of 60 every two weeks starting in January 2020. OneWeb will launch over 30 satellites later this year. We could soon see thousands of satellites working in tandem to supply internet access for even the poorest and most remote populations on the planet.

But thats only if things work out. Some researchers are livid because they fear these objects will disrupt astronomy research. Worse is the prospect of a collision that could cascade into a catastrophe of millions of pieces of space debris, making satellite services and future space exploration next to impossible. Starlinks near-miss with an ESA weather satellite in September was a jolting reminder that the world is woefully unprepared to manage this much orbital traffic. What happens with these mega-constellations this decade will define the future of orbital space.

Neel V. Patel

Google has provided the first clear proof of a quantum computer outperforming a classical one.

Yoshi Sodeoka

Quantum computers store and process data in a way completely differently from the ones were all used to. In theory, they could tackle certain classes of problems that even the most powerful classical supercomputer imaginable would take millennia to solve, like breaking todays cryptographic codes or simulating the precise behavior of molecules to help discover new drugs and materials.

There have been working quantum computers for several years, but its only under certain conditions that they outperform classical ones, and in October Google claimed the first such demonstration of quantum supremacy. A computer with 53 qubitsthe basic unit of quantum computationdid a calculation in a little over three minutes that, by Googles reckoning, would have taken the worlds biggest supercomputer 10,000 years, or 1.5 billion times as long. IBM challenged Googles claim, saying the speedup would be a thousandfold at best; even so, it was a milestone, and each additional qubit will make the computer twice as fast.

However, Googles demo was strictly a proof of conceptthe equivalent of doing random sums on a calculator and showing that the answers are right. The goal now is to build machines with enough qubits to solve useful problems. This is a formidable challenge: the more qubits you have, the harder it is to maintain their delicate quantum state. Googles engineers believe the approach theyre using can get them to somewhere between 100 and 1,000 qubits, which may be enough to do something usefulbut nobody is quite sure what.

And beyond that? Machines that can crack todays cryptography will require millions of qubits; it will probably take decades to get there. But one that can model molecules should be easier to build.

Gideon Lichfield

We can now run powerful AI algorithms on our phones.

Julia Dufoss

AI has a problem: in the quest to build more powerful algorithms, researchers are using ever greater amounts of data and computing power, and relying on centralized cloud services. This not only generates alarming amounts of carbon emissions but also limits the speed and privacy of AI applications.

But a countertrend of tiny AI is changing that. Tech giants and academic researchers are working on new algorithms to shrink existing deep-learning models without losing their capabilities. Meanwhile, an emerging generation of specialized AI chips promises to pack more computational power into tighter physical spaces, and train and run AI on far less energy.

These advances are just starting to become available to consumers. Last May, Google announced that it can now run Google Assistant on users phones without sending requests to a remote server. As of iOS 13, Apple runs Siris speech recognition capabilities and its QuickType keyboard locally on the iPhone. IBM and Amazon now also offer developer platforms for making and deploying tiny AI.

All this could bring about many benefits. Existing services like voice assistants, autocorrect, and digital cameras will get better and faster without having to ping the cloud every time they need access to a deep-learning model. Tiny AI will also make new applications possible, like mobile-based medical-image analysis or self-driving cars with faster reaction times. Finally, localized AI is better for privacy, since your data no longer needs to leave your device to improve a service or a feature.

But as the benefits of AI become distributed, so will all its challenges. It could become harder to combat surveillance systems or deepfake videos, for example, and discriminatory algorithms could also proliferate. Researchers, engineers, and policymakers need to work together now to develop technical and policy checks on these potential harms.

Karen Hao

A technique to measure the privacy of a crucial data set.

In 2020, the US government has a big task: collect data on the countrys 330 million residents while keeping their identities private. The data is released in statistical tables that policymakers and academics analyze when writing legislation or conducting research. By law, the Census Bureau must make sure that it cant lead back to any individuals.

But there are tricks to de-anonymize individuals, especially if the census data is combined with other public statistics.

So the Census Bureau injects inaccuracies, or noise, into the data. It might make some people younger and others older, or label some white people as black and vice versa, while keeping the totals of each age or ethnic group the same. The more noise you inject, the harder de-anonymization becomes.

Differential privacy is a mathematical technique that makes this process rigorous by measuring how much privacy increases when noise is added. The method is already used by Apple and Facebook to collect aggregate data without identifying particular users.

But too much noise can render the data useless. One analysis showed that a differentially private version of the 2010 Census included households that supposedly had 90 people.

If all goes well, the method will likely be used by other federal agencies. Countries like Canada and the UK are watching too.

Angela Chen

Researchers can now spot climate changes role in extreme weather.

Yoshi Sodeoka

Ten days after Tropical Storm Imelda began flooding neighborhoods across the Houston area last September, a rapid-response research team announced that climate change almost certainly played a role.

The group, World Weather Attribution, had compared high-resolution computer simulations of worlds where climate change did and didnt occur. In the former, the world we live in, the severe storm was as much as 2.6 times more likelyand up to 28% more intense.

Earlier this decade, scientists were reluctant to link any specific event to climate change. But many more extreme-weather attribution studies have been done in the last few years, and rapidly improving tools and techniques have made them more reliable and convincing.

This has been made possible by a combination of advances. For one, the lengthening record of detailed satellite data is helping us understand natural systems. Also, increased computing power means scientists can create higher-resolution simulations and conduct many more virtual experiments.

These and other improvements have allowed scientists to state with increasing statistical certainty that yes, global warming is often fueling more dangerous weather events.

By disentangling the role of climate change from other factors, the studies are telling us what kinds of risks we need to prepare for, including how much flooding to expect and how severe heat waves will get as global warming becomes worse. If we choose to listen, they can help us understand how to rebuild our cities and infrastructure for a climate-changed world.

James Temple

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10 Breakthrough Technologies 2020 - MIT Technology Review

Emerson College student with progeria heartened that first drug treatment could be approved soon – The Boston Globe

Waldron has already lived considerably longer she turns 19 on March 1. She credits lonafarnib, an experimental medication shes taken since 2007 in clinical trials at Boston Childrens Hospital. A California drug firm plans to complete its application for approval by March 31, with the hope of a favorable ruling from the Food and Drug Administration by years end. It would be the first approved drug for the ultra-rare disease.

Its been proven that it helps in extending life, Waldron, a Deerfield native, said recently over hot chocolate at Caffe Nero near Emerson. Im almost 19. The life span is technically 14. A winsome smile brightened her face. Looks like its doing a good job.

Since 2007, Childrens Hospital has run four clinical trial of lonafarnib. Waldron has participated in all four, and researchers say the results are encouraging.

In perhaps the most compelling finding, a study published by the Journal of the American Medical Association in 2018 reported that children with progeria who took lonafarnib capsules twice a day had a dramatically lower mortality rate than those who didnt.

After slightly more than two years, one in 27 children who took lonafarnib, or 3.7 percent, had died compared with nine in 27 who didnt get it, or 33 percent, according to the article by a team of researchers from the Progeria Research Foundation, Brown University, and Childrens Hospital. Lonafarnib appeared to slow the progression of cardiovascular disease, although it had little or no effect on other symptoms, including stiff joints, stunted growth, wrinkled skin, and loss of body fat and hair.

The data looks fantastic, said Dr. Leslie Gordon, lead author of the JAMA study and medical director and cofounder of the Progeria Research Foundation, the Peabody-based nonprofit that funded the trials. Youve got a fatal childhood disease with no treatment, and youve shown a survival benefit.

For Gordon, a professor of pediatric medicine at Browns medical school who practices at Boston Childrens Hospital and Hasbro Childrens Hospital in Providence, the quest to treat progeria is profoundly personal.

Her son, Sam Berns, a Foxborough High School junior, died of progeria in 2014 at age 17. Like Waldron, he began taking lonafarnib in 2007 in the clinical trials. An avid sports fan who played the snare drum in the Foxborough High School marching band, he was the subject of the 2013 HBO documentary Life According to Sam.

Gordon had never heard of progeria when Sam, her only child, was diagnosed with it at 22 months. She has since become an authority. In 2003, she was on the research team led by Dr. Francis S. Collins, director of the National Institutes of Health, that discovered the defective gene that causes the disease. She cofounded the progeria foundation with her husband and sister.

The genetic mutation that causes progeria results in an overabundance of the protein progerin. A buildup of progerin occurs within a cell in normal aging, but the rate of accumulation is dramatically accelerated in children with the disease. Progeria has no effect on a childs intellect, as anyone who meets Waldron who took an Advanced Placement class in European history in high school and rhapsodizes about Michelangelo can tell in an instant.

Lonafarnib was originally developed by the pharmaceutical giant Merck as a potential treatment for cancer. But researchers found that it can reverse an abnormality in cells of laboratory mice with progeria. Merck has licensed it to Eiger BioPharmaceuticals, a small drug maker in Palo Alto, Calif. David Cory, chief executive of Eiger, says the company has hired a chief commercial officer and a vice president of medical affair in anticipation of FDA approval.

Researchers are working on other potential treatments, including one that targets the genetic root of the disease. David Liu, a chemistry professor affiliated with the Broad Institute, Harvard University, and the Howard Hughes Medical Institute, recently announced that he and a team of scientists had used a new form of genome editing to correct the DNA mutation that caused the disorder in mice, extending their lives.

Waldron, who serves as an ambassador for the progeria foundation, said she was diagnosed with the disease when she was about 2. Her mother, a housekeeper at an assisted living facility, and her father, a solar energy contractor, were worried because she wasnt growing or gaining weight, and her hair was falling out.

Waldron realized she had progeria as an adolescent when she went on the foundations website and saw pictures of kids who looked like her, she said.

Obviously, I knew that I was different before that, she said. But it wasnt an awareness I-have-progeria thing until at a certain point.

The disease has hardly stopped her. She ran for the cross-country and track teams at the public Frontier Regional High School in Deerfield. She played violin in the middle school orchestra and cello in the high school orchestra.

She has met about a dozen other children with progeria from around the country at family weekends at the nonprofit Hole in the Wall Gang Camp in Connecticut for seriously ill children and their families.

When she started considering colleges, Waldron said, she had no interest in going to school in Boston. But she fell in love with the city on a visit to Emerson.

You can walk down the street or hop on a train and go anywhere, she said, citing the North End as one of her favorites places.

I have great friends," she added. "I always have.

Emerson has made several accommodations for her. For example, the college provides a stool for her to rest her feet on when she sits at a desk in her four classes. The handle on her wardrobe in her dorm room was lowered so she could reach it more easily.

Waldron says she generally feels fine despite problems with her joints. She has dislocated her right shoulder four times doing ordinary tasks, such as reaching for a light switch.

None of this has dimmed her spirit for adventure.

Meghan has a very strong personality. Shes driven, her father, Bill Waldron, said in a video posted last year on the progeria foundations Facebook page. I dont think she pays attention to the fact that she has progeria.

Indeed, after graduating from high school in June, she traveled in Europe alone for a month. The initial attraction was seeing Anne-Marie, a singer and occasional Ed Sheeran collaborator, perform in London. But Waldron decided she also wanted to experience Renaissance art. She visited Milan, Florence, Rome, Paris, and Dublin, staying in youth hostels along the way.

Waldrons parents were nervous, she said. She was, too, but only briefly.

There was a point of about five minutes when my parents said goodbye and I was getting on the plane where I started freaking out, she said, laughing. But then I was like, Oh, well. And then I was fine.

Jonathan Saltzman can be reached at jonathan.saltzman@globe.com

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Emerson College student with progeria heartened that first drug treatment could be approved soon - The Boston Globe

Gene ID’d as potential therapeutic target for dementia in Parkinson’s – Washington University School of Medicine in St. Louis

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Targeting gene linked to Alzheimers may reduce dementia risk in Parkinsons

Clumps of the Parkinsons protein alpha-synuclein (red) are visible inside neurons (green) in the brain of a mouse. Researchers at Washington University School of Medicine in St. Louis have discovered that the genetic variant APOE4 long linked to dementia spurs the spread of harmful clumps of Parkinsons proteins through the brain. The findings suggest that therapies that target APOE might reduce the risk of dementia for people with Parkinsons disease.

Dementia is one of the most debilitating consequences of Parkinsons disease, a progressive neurological condition characterized by tremors, stiffness, slow movement and impaired balance. Eighty percent of people with Parkinsons develop dementia within 20 years of the diagnosis, and patients who carry a particular variant of the gene APOEare at especially high risk.

In new research, scientists at Washington University School of Medicine in St. Louis have found a clue to the link between Parkinsons, APOEand dementia. They discovered that harmful Parkinsons proteins spread more rapidly through the brains of mice that have the high-risk variant of APOE, and that memory and thinking skills deteriorate faster in people with Parkinsons who carry the variant. The findings, published Feb. 5 in Science Translational Medicine, could lead to therapies targeting APOEto slow or prevent cognitive decline in people with Parkinsons.

Dementia takes a huge toll on people with Parkinsons and their caregivers, said Albert (Gus) Davis, MD, PhD, an assistant professor of neurology and the studys lead author. The development of dementia is often what determines whether someone with Parkinsons is able to remain in their home or has to go into a nursing home.

An estimated 930,000 people in the U.S. live with Parkinsons. The disease is thought to be caused by toxic clumps of a protein called alpha-synuclein that build up in a part of the brain devoted to movement. The clumps damage and can kill brain cells.

Cognitive problems tend to arise many years after the motor symptoms. The protein clusters implicated in movement problems also are linked with dementia, but how this happens is not clear. Davis and his colleagues including senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of theDepartment of Neurology saw a clue in the risky nature of APOE.

A variant of APOE known as APOE4 raises the risk of Alzheimers disease threefold to fivefold. Like Parkinsons, Alzheimers is a neurodegenerative condition caused by the spread of toxic protein clusters throughout the brain, although some of the proteins involved are different. APOE4 increases the chance of Alzheimers dementia partly because it spurs Alzheimers proteins to collect into clumps that injure the brain. The researchers suspected that APOE4 similarly triggers the growth of toxic clusters of Parkinsons proteins.

Studying mice with a form of alpha-synuclein prone to clumping, Davis, Holtzman and colleagues genetically modified the mice to carry human variants of APOE APOE2, APOE3 or APOE4 or no APOE at all.

The researchers found that APOE4 mice had more alpha-synuclein clusters than APOE3 orAPOE2mice. Further experiments showed that the clumps spread more widely in APOE4 mice as well. Together, the findings showed that APOE4 was directly involved in exacerbating signs of disease in the mices brains.

What really stood out is how much less affected the APOE2 mice were than the others, Davis said. It actually may have a protective effect, and we are investigating this now. If we do find that APOE2 is protective, we might be able to use that information to design therapies to reduce the risk of dementia.

To study the effect of APOEvariants on dementia in people with Parkinsons, the researchers analyzed publicly available data from three separate sets of people with Parkinsons. Two of the cohorts one from the Parkinsons Progression Markers Initiative, with 251 patients, and the other from the Washington University Movement Disorders Center, with 170 patients had been followed for several years. In both cohorts, cognitive skills declined faster in people with APOE4 than in those with APOE3. People with two copies of APOE2 are very rare, but none of the three patients in the group with two copies of APOE2showed any cognitive decline over the period of the study.

The third cohort, fromthe NeuroGenetics Research Consortium, was made up of 1,030 people with Parkinsons whose cognitive skills had been evaluated just once. The researchers found that people with APOE4 in the cohorthad developed cognitive problems at a younger age and had more severe cognitive deficits at the time they were evaluated than people with APOE3 or APOE2.

Parkinsons is the most common, but there are other, rarer diseases that also are caused by alpha-synuclein aggregation and also have very limited treatment options, Davis said. Targeting APOE with therapeutics might be a way to change the course of such diseases.

APOE doesnt affect the overall risk of developing Parkinsons or how quickly movement symptoms worsen, so an APOE-targeted therapy might stave off dementia without doing anything for the other symptoms. Even so, it could be beneficial, Davis said.

Once people with Parkinsons develop dementia, the financial and emotional costs to them and their families are just enormous, Davis said. If we can reduce their risk of dementia, we could dramatically improve their quality of life.

Davis AA, Inman CE, Wargel ZM, Dube U, Freeberg BM, Galluppi A, Haines JN, Dhavale DD, Miller R, Choudhury FA, Sullivan PM, Cruchaga C, Perlmutter JS, Ulrich JD, Benitez BA, Kotzbauer PT, Holtzman DM. APOE Genotype Regulates Pathology and Disease Progression in Synucleinopathy. Science Translational Medicine. Feb. 5, 2020. DOI: 10.1126/scitranslmed.aay3069

This work was supported by an American Academy of Neurology/American Brain Foundation (Clinical Research Training Fellowship); the BrightFocus Foundation; the Mary E. Groff Charitable Trust; the Dobbins Family Fund; the Foundation for Barnes-Jewish Hospital (Elliot Stein Family Fund); the Riney Foundation; the American Parkinson Disease Association; the Greater St. Louis Chapter of the American Parkinson Disease Association; The JPB Foundation; and the National Institutes of Health (NIH), grant numbers K08NS101118, R01AG044546, RF1AG053303, RF1AG058501, U01AG052411, U01AG058922, NS075321, NS097799, R01NS090934 and R01AG047644.

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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Gene ID'd as potential therapeutic target for dementia in Parkinson's - Washington University School of Medicine in St. Louis

Genialis and Oncologie Collaborate on Precision Medicine Initiative in Gastric Cancer – Business Wire

SAN RAMON, Calif. & WALTHAM, Mass.--(BUSINESS WIRE)--Genialis, a leader in applied data science for the development of precision medicines, today announced a collaborative partnership with Oncologie, an international, clinical-stage biopharma developing next-generation immunotherapies for cancer. Initial activities will focus on the use of Genialis Expressions software platform and analytics IP with Oncologies clinical and translational expertise to refine patient stratification methodologies.

We are incredibly excited to work with Genialis on this cutting-edge, precision medicine project. To be able to better understand the patients tumor microenvironment phenotype and how it is related to patient benefit represents a key objective for the future success of our company, says Oncologie CEO Laura Benjamin.

Early work between the two companies has thus far focused on modeling gene expression signatures predictive of treatment for gastric cancer. The patent-pending enhanced methodology will further Oncologies clinical development plans to expand beyond gastric cancer to other tumor microenvironment phenotypes.

One of the most encouraging trends in drug development is innovation around integrating and interrogating diverse datasets. Data from historical literature, public population studies, first in human trials, et cetera, can be leveraged to answer significant questions on how to make safe and effective treatments more readily available to patients fighting debilitating and deadly diseases, says Genialis CEO Rafael Rosengarten. Our work in data science requires a great deal of artistry in addition to technology. And benefits from hand-in-hand collaboration with biology domain experts, which makes this opportunity with Oncologie so special. Right from the start, we knew we shared a vision and a commitment to the process.

This week Genialis will present its work on predictive models for patient stratification at the Precision Medicine World Conference in Santa Clara, CA on January 22.

About Oncologie, Inc.

Oncologie, Inc. is an innovative biopharmaceutical company committed to delivering better outcomes for cancer patients through improved approaches to patient selection and clinical trial design. Our current pipeline includes clinical programs that improve treatment outcomes by modulating the tumor micro-environment and enhancing the immune response to targeting cancer cells. From its headquarters in Boston, Massachusetts and Shanghai, China, Oncologie is working with global partners to acquire and develop innovative drugs for cancer patients around the world. For more information on Oncologie, Inc., please visit http://www.oncologie.international.

About Genialis

Genialis is a data science and drug discovery company focused on new ways to treat disease. Blending computational biology and AI-based methods, Genialis merges and models data at the intersection of clinical and translational medicine. Genialis is trusted by biopharma and big pharma alike, to identify targets, predict biomarkers and optimally position novel drugs. Together, Genialis and its partners work to bring improved solutions to drug discovery to change people's lives.

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Genialis and Oncologie Collaborate on Precision Medicine Initiative in Gastric Cancer - Business Wire

Surprises in Cell Codes Reveal Information Goes Far Beyond DNA – Discovery Institute

Information is the stuff of life. Not limited to DNA, information is found in most biomolecules in living cells. Here are some recent developments.

Certain forms of sugars (polysaccharides called chitosans) trigger the immune system of plants. Biologists at the University of Mnster are deciphering the sugar code. They describe the variables in chitosans that constitute a signaling system.

Chitosans consist of chains of different lengths of a simple sugar called glucosamine. Some of these sugar molecules carry an acetic acid molecule, others do not. Chitosans therefore differ in three factors: the chain length and the number and distribution of acetic acid residues along the sugar chain. For about twenty years, chemists have been able to produce chitosans of different chain lengths and with different amounts of acetic acid residues, and biologists have then investigated their biological activities. [Emphasis added.]

These polysaccharides, also found in animals, are perhaps the most versatile and functioning biopolymers, the scientists say. If they can learn to decipher this complex code, they might find ways to protect plants without the use of pesticides.

DNA is becoming known as a more of a team member in a society of biomolecules. In some ways, it is more a patient than a doctor. It gets operated on by numerous machines that alter its message. One of the most important doctors that operates on RNA transcripts is the spliceosome, says a review article in The Scientist about alternative splicing. This complex molecular machine can multiply the messages in the coding regions of DNA by cutting out introns and stitching coded parts called exons together in different ways.

The process of alternative splicing, which had first been observed 26 years before the Human Genome Project was finished, allows a cell to generate different RNAs, and ultimately different proteins, from the same gene. Since its discovery, it has become clear that alternative splicing is common and that the phenomenon helps explain how limited numbers of genes can encode organisms of staggering complexity. While fewer than 40 percent of the genes in a fruit fly undergo alternative splicing, more than 90 percent of genes are alternatively spliced in humans.

Astoundingly, some genes can be alternatively spliced to generate up to 38,000 different transcript isoforms, and each of the proteins they produce has a unique function.

The discovery of splicing seemed bizarre from an evolutionary perspective, the authors say, recalling obsolete ideas about junk DNA. It seemed weird and wasteful that introns were being cut out of transcripts by the spliceosome. Then, the ENCODE project found that the vast majority of non-coding DNA was transcribed, giving these seemingly nonfunctional elements an essential role in gene expression, as evidence emerged over the next few years that there are sequences housed within introns that can help or hinder splicing activity.

This article is a good reminder that evolutionary assumptions hinder science. Once biochemists ridded themselves of the evolutionary notion of leftover junk in the genetic code, a race was on to understand the role of alternative splicing.

Understanding the story behind each protein in our bodies has turned out to be far more complex than reading our DNA. Although the basic splicing mechanism was uncovered more than 40 years ago, working out the interplay between splicing and physiology continues to fascinate us. We hope that advanced knowledge of how alternative splicing is regulated and the functional role of each protein isoform during development and disease will lay the groundwork for the success of future translational therapies.

Another discovery that is opening doors to research opportunities comes from the University of Chicago. Darwin-free, they announce a fundamental pathway likely to open up completely new directions of research and inquiry. Biologists knew about how methyl tags on RNA transcripts regulate the ways they are translated. Now, Professor Chuan He and colleagues have found that some RNAs, dubbed carRNAs, dont get translated at all. Instead, they controlled how DNA itself was stored and transcribed.

This has major implications in basic biology, He said. It directly affects gene transcriptions, and not just a few of them. It could induce global chromatin change and affects transcription of 6,000 genes in the cell line we studied.

Dr. He is excited about the breakthrough. The conceptual change in how RNA regulates DNA offers an enormous opportunity to guide medical treatments and promote health. Take a look at this design-friendly quote:

The human body is among the most complex pieces of machinery to exist. Every time you so much as scratch your nose, youre using more intricate engineering than any rocket ship or supercomputer ever designed. Its taken us centuries to deconstruct how this works, and each time someone discovers a new mechanism, a few more mysteries of human health make sense and new treatments become available.

Remember the evolutionary myth that jumping genes were parasites from our evolutionary past that learned how to evade the immune system? A discovery at the Washington University School of Medicine changes that tune, saying, Jumping genes help stabilize DNA folding patterns. These long-misunderstood genes thought by some evolutionists to be sources of novel genetic traits actually function to provide genomic stability.

Jumping genes bits of DNA that can move from one spot in the genome to another are well-known for increasing genetic diversity over the long course of evolution. Now, new research at Washington University School of Medicine in St. Louis indicates that such genes, also called transposable elements, play another, more surprising role: stabilizing the 3D folding patterns of the DNA molecule inside the cells nucleus.

It appears that by moving around, these genes can preserve the structure of DNA while not altering its function. (Note: the evolution they speak of appears to be microevolution, which is not controversial; hear Jonathan Wells discuss this on ID the Future.)

According to the researchers, this redundancy makes the genome more resilient. In providing both novelty and stability, jumping genes may help the mammalian genome strike a vital balance allowing animals the flexibility to adapt to a changing climate, for example, while preserving biological functions required for life.

Lead author Ting Wang says this gives insight into why coding regions between different animals vary in structure.

Our study changes how we interpret genetic variation in the noncoding regions of the DNA, Wang said. For example, large surveys of genomes from many people have identified a lot of variations in noncoding regions that dont seem to have any effect on gene regulation, which has been puzzling. But it makes more sense in light of our new understanding of transposable elements while the local sequence can change, but the function stays the same.

So while evolutionists had expected junk and simplicity, Wang says the opposite has occurred. We have uncovered another layer of complexity in the genome sequence that was not known before. Now, more discoveries are likely to flow from intelligent designs expectation that a closer look reveals more complexity.

In another recent podcast at ID the Future honoring the late Phillip E. Johnson, Paul Nelson likened a graph of mounting discoveries about life to a sharply rising mountain range. Darwin proposed his theory on the flatlands, unaware of the peaks his theory would have to explain. In the last fifty years, scientists have encountered mountain after mountain of complexity in life that evolutionary theory never anticipated back out there on the flatlands. We cant see the top of the mountains yet, but we know that were still not there, and we wont be for a long, long time, Nelson says. As we witness scientists continuing up the mountains, we anticipate with awe more wonders of design that will likely come to light in the next decade.

Image: Interior of a cell, courtesy of Illustra Media.

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Surprises in Cell Codes Reveal Information Goes Far Beyond DNA - Discovery Institute