Category Archives: Genetic Medicine

SAN DIEGO, Oct. 15, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that a study led by scientists and clinicians from the Institute for Human Genetics at the UCSF School of Medicine and the Department of Pediatrics at the University of Colorado School of Medicine and published in bioRxiv used Bionanos proprietary genome imaging technology to identify novel disease causing variants in patients with three different genetic diseases and in a diverse control dataset of 154 individuals. The study found that Bionano's Saphyr System was able to comprehensively analyze complex genome structures called segmental duplications and helped identify several novel structural variations associated with each disease causing locus increasing the understanding of these diseases.

Segmental duplications are large segments of repetitive sequences tens to hundreds of thousands of base pairs in size. Short-read and long-read sequencing technologies cannot span these large segments of the genome. Only Bionanos optical mapping technology can image single molecules that are so long that they span the segmental duplications. These repetitive sequences can interact with each other when sperm or eggs are created and their rearrangement can cause severe genetic disease. Some of the most common of such diseases are microdeletions at 7q11.23, also known as Williams-Beuren syndrome (WBS), 15q13.3 microdeletion syndrome, 16p12.2 microdeletion syndrome and 22q11.2 deletion syndrome, also known as DiGeorge syndrome.

This study, published in bioRxiv, provides a population-level analysis of segmental duplications in 154 people and in patients with WBS, 15q13.3, and 16p12.2 microdeletion syndromes. Several novel SVs were detected for each locus, and the exact disease causing rearrangement was determined with much higher accuracy than was formerly possible without Saphyr. As previously announced, a recent publication in the journal Nature published on July 22, 2020 also discussed the unique contribution of Bionanos optical mapping technology to understanding the genetic causes of DiGeorge syndrome.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented, The microdeletion and microduplication syndromes are common genetic disorders, yet the exact genomic structures that cause them have been difficult or impossible to characterize with current sequencing-based methods. Even though microdeletion syndromes are commonly represented by hallmark features, in many cases a wide variability in clinical features is observed. Being able to understand and measure the subtle structural differences in microdeletions among different patients could allow for better clinical or therapeutic management. An increasing number of studies have relied on Bionanos Saphyr system to characterize disease-causing structural variants that could not be correctly analyzed with other molecular techniques. We will continue to make our technology available to researchers everywhere who want to greatly expand the capabilities of their genomic analysis.

The publication is available at https://www.biorxiv.org/content/10.1101/2020.04.30.071449v1.full

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the contribution of Bionanos technology to the analysis or understandings of microdeletion syndromes and future development of better clinical or therapeutic management for such diseases; the effectiveness and utility of Bionanos technology in clinical settings; Saphyrs capabilities in comparison to other genome analysis technologies; the benefits of Bionanos optical mapping technology and its ability to facilitate genomic analysis in future studies; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Bionano Genomics' Saphyr System Shown to be Indispensable for the Analysis of Certain Genetic Disease Causing Variants - GlobeNewswire

By Deborah Borfitz

October 15, 2020| The Bio-IT World Conference & Expo closed out with a plenary keynote presentation on preventive genomics by Robert Green, M.D., professor of medicine at Harvard Medical School and a physician-scientist who directs the G2P Research Program at Brigham and Womens Hospital and the Broad Institute. Data-sharing difficulties were a recurring theme at this years conference but, as the COVID-19 Host Genetics Initiative has demonstrated, it is possible to combine genomic data to rapidly explore markers of disease, he says. But far more daily deaths are caused by cancer and cardiovascular diseasenot the pandemic virusand 59 of the causal genes are already known and actionable.

Genomic information is rarely incorporated into clinical care partly because labs, not care providers, are doing most of the testing and doctors are unclear if the benefits outweigh the costs and risks, says Green. The clinical value of DNA sequencing is also unproven, although its the central feature of personalized medicine programs that have been popping up around the country.

Green presented lessons learned from the MedSeq, exploring the impacts of incorporating genomic sequencing into everyday medicine for people with and without a suspected genetic cardiac disease, and BabySeq, testing methods for integrating sequencing into the care of newborns. Both are randomized trials funded by the National Institutes of Health.

MedSeq involved primary care physicians taking comprehensive family histories on participants with or without the addition of one-page genomic reports and following their outcomes. Reports from preventive genomic testing focused on defined, disease-specific variants with the highest clinical actionability, says Green, as distinct from indication-based testing looking at a wider universe of variants known or suspected of being pathogenic.

Notably, Green says, neither doctors nor patients experienced test-related anxietyeven when a monogenetic risk variant was discovered. In 100 individuals, 20% were found to carry a dominant mutation for a monogenetic condition. In fact, among the top four genetic mutations, sequencing often discovered ongoing disease that the healthcare system had missed.

Participating doctors, after only six hours of training, did not make any errors in communicating the results, adds Green. Healthcare spending six months post-disclosure was higher but not extraordinarily more. Two years later, 22% had been reclassified (e.g., variant of uncertain significance now likely benign or likely pathogenic variant now pathogenic).

In the smaller BabySeq Project, 11% of participants were identified as having monogenetic disease risk, Green says. As with MedSeq, a substantial number with genetic mutations already had phenotypic evidence of disease previously missed by their healthcare providers.

BabySeq additionally revealed no difference in bonding or vulnerability, says Green. Catastrophic distress is not an obstacle [to sequencing], as has often been suggested. The falling cost of genomic sequencing and interpretation should further improve the benefit-to-cost ratio.

Exactly how often does sequencing reveal something important? Herere the stats from Green: 91% of the time for recessive mutations, 80% for atypical responses to medications, 15% for dominant mutation, and 50% for elevated polygenic risk specific to at least one condition such as diabetes or cancer.

Polarizing Topic

The Mass General Brigham Biobank, which looked for the 59 genes linked to disease, has identified such mutations in over 350 of the roughly 36,000 people it has sequenced. In 75% if those cases, the mutations were linked to either cardiovascular disease or cancer and the individuals had no idea they were carrying mutations, says Green.

A significant number did not even want to know of their risk, he adds. A similarly high number met National Comprehensive Cancer Center criteria for genetic testing but had never before been tested.

The Preventive Genomics Clinic at Brigham and Womens Hospital, staffed by genetics experts and counselors, offers individuals a menu of testing options (whole genome sequencing as well as smaller panels) and also gives patients the option of being seen via telemedicine. The heart-touching stories shared on its website include a man nudged by discovered mutations to finally get a colonoscopy, revealing two cancerous lesions that were subsequently extracted, and another with worsening heart disease who learned the underlying cause was Fabry diseasea rare but treatable condition.

Genomics is a notoriously polarizing subject, Green says. The challenge in convincing the skeptics is that genomics crosses multiple therapeutic domains and testing needs to be repeated over individuals lifetime.

The exceptionalism of genomics is sometimes misplaced, he later adds, referring to the disproportionate amount of fear about misuse of genetic information relative to psychological or infectious disease data. Its perfectly possible for large groups to share genomic data that is not identifiable. Its not full-proof, but its [technically] feasible.

Federal genetic privacy laws prevent genetics-based discrimination by employers and health insurers, Green says. In July, Florida became the first state in the nation to enact a DNA privacy law that also prohibits life, disability and long-term care insurance companies from using genetic tests for coverage purposes.

Editors Note: Even if you missed the start of the event, Bio-IT World Conference & Expo virtualis still live. Register nowfor on-demand presentations.

Continued here:
Proving The Value Of Preventive Genomics - Bio-IT World

BALA CYNWYD, Pa., Oct. 13, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases,today announced the formation of its Scientific Advisory Board (SAB). Larimars SAB is comprised of distinguished research scientists, professors and industry experts recognized as key opinion leaders in the fields of rare disease, pediatrics and mitochondrial disease.

Larimar is privileged to have this group of prestigious, multidisciplinary advisors who are committed to advancing the research and development of CTI-1601 for Friedreichs ataxia, said Nancy M. Ruiz, MD, FACP, FIDSA, Chief Medical Officer of Larimar Therapeutics. Their scientific perspectives will be invaluable to determine our strategic scientific pathway and support the development of other potential treatments for complex rare diseases to help fill unmet medical needs in this space.

Formalizing the SAB adds to our recent accomplishments, which include resuming our Phase 1 clinical trial of CTI-1601 for Friedreichs ataxia and receiving a positive opinion on orphan drug designation for CTI-1601 from the European Medicines Agencys Committee for Orphan Medicinal Products, said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar Therapeutics. This progress helps position Larimar for success as we continue to execute our strategy of developing treatments for complex rare diseases.

The members of Larimars SAB are as follows:

About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq:LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. The companys lead compound, CTI-1601, is currently being evaluated in a Phase 1 clinical program in the U.S. as a potential treatment for Friedreichs ataxia, a rare and progressive genetic disease. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.

Investor Contact:Joyce AllaireLifeSci Advisors, LLC(212) 915-2569jallaire@lifesciadvisors.com

Media Contact:Gina Cestari6 Degrees(917) 797-7904gcestari@6degreespr.com

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Larimar Therapeutics Announces Formation of Scientific Advisory Board - GlobeNewswire

Along with the woolly mammoth and the giant ground sloth, the sabre-toothed cats were probably among the most famous animals that lived during the Pleistocene Epoch and went extinct before the end of last ice age. Over the years, sabre-toothed cats have also been the subject of many research projects.

Now, for the first time, researchers from the University of Copenhagen have succeeded in mapping the entire nuclear genome of a sabre-toothed cat, the scimitar-toothed cat Homotherium latidens. Their DNA study reveals what genes were highly selected upon and important in evolution of the species.

Their genetic makeup hints towards scimitar-toothed cats being highly skilled hunters. They likely had very good daytime vision and displayed complex social behaviours. They had genetic adaptations for strong bones and cardiovascular and respiratory systems, meaning they were well suited for endurance running. Based on this, we think they hunted in a pack until their prey reached exhaustion with an endurance-based hunting-style during the day light hours, says co-first author Michael Westbury, Postdoc at the Section for Evolutionary Genomics, GLOBE Institute, University of Copenhagen.

Abundant species

The researchers extracted DNA from a Homotherium fossil recovered from Pleistocene permafrost sediments near Dawson City, Yukon Territory, Canada. This specimen was so old it could not be dated using conventional radio-carbon dating meaning that it was at least 47.5 thousand years old.

They then used a variety of modern genomic sequencing techniques to map the entire genome of the fossil. They used complex comparative analyses to modern living cat species such as lions and tigers and showed that this sabre-toothed cat were very genetically diverse, relative to modern cat species.

We know that genetic diversity correlates to how many of a given species that exists. Based on this, our best guess is that there were a lot of these big cats around. This also makes perfect sense given that their fossils have been found on every single continent except Australia and Antarctica, says Michael Westbury.

Synergies with medical research and bioinformatics

Their analysis also showed that the sabre-toothed cat is very distantly related to all modern cats. They diverged from them around least 22.5 million years ago. In comparison, humans and gibbons split between 15 and 20 million years ago.

This was an extremely successful family of cats. They were present on five continents and roamed the earth for millions of years before going extinct. The current geological period is the first time in 40 million years that earth has lacked sabretooth predators. We just missed them says co-first author Ross Barnett.

The researchers also emphasize that their study is an example of how different fields of research can benefit from each other. They hope to see similar bioinformatics methods used on many other extinct animals in the future.

Modern advancements within medicine and genetic research means that the sequencing methods are a lot better for us now than they were just a few years ago. On top of that, we know what specific genes are associated with in animals and humans from medical research. This means that we can infer a lot of things about extinct animals as we have done here. You could say that the fast progression of medical research has made this study possible, says professor Tom Gilbert.

UNIVERSITY OF COPENHAGEN THE FACULTY OF HEALTH AND MEDICAL SCIENCES

Header Image Credit : University of Copenhagen

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DNA Study Reveals Insights About the Scimitar-Toothed Cat - HeritageDaily

COPENHAGEN, Denmark, Oct. 13, 2020 /PRNewswire/ -- Novo Seeds, the early stage investment and company creation team of Novo Holdings, today announced an investment in Rappta Therapeutics ("Rappta"), an emerging biotech company focused on developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). The investment is a part of a EUR 9M series A financing round.

PP2A is a critical enzyme regulating protein de-phosphorylation and a key tumor suppressor which to date has been very difficult to target pharmaceutically. Rappta has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A. As a result of PP2A's central role in the regulation of protein de-phosphorylation, Rappta's PP2A-reactivating technologies offer the potential to develop multiple lead compounds and build a platform for a new class of anti-cancer drugs.

Rappta has assembled a strong scientific, management and commercial team based in Finland and the US. Rappta's scientific team, led by CSO and co-founder, Professor Goutham Narla, Division Chief of Genetic Medicine at the University of Michigan, represents world-leading expertise in PP2A. The scientific team has published seminal papers onthe structural, functional and biological mechanisms of PP2A inactivation in human cancer. The team will be supported by the Scientific Advisory Board lead by Dr. William Hahn, a Professor of Medicine at the Harvard Medical School and the Chief Scientific Officer at the Dana-Farber Cancer Institute.

As a resut of the financing, Jeroen Bakker, Principal at Novo Seeds will join the Board.Other investors in the Series A round include Novartis Venture Fund ("NVF"), Advent Life Sciences ("Advent") and one family office.

Jeroen Bakker, Principal, Novo Seeds, said: "We are impressed by the team's pioneering work in PP2A-reactivating technologies. Novo Seeds' strategy is to back teams from all over the globe with world class science and attract other bluechip investors to help transform these entreprises into successful business in the Nordics. We are very pleased to see renowned investors such as NVF and Advent investing in the region. We look forward to working with them as we support Rappta's world-leading team translate their scientific and medical expertise in phosphatase biology into a clinical oncology biotech."

Mikko Mannerkoski, CEO and co-founder of Rappta Therapeutics, commented: "We are very pleased to attract such a strong syndicate of international investors which validates our approach to developing novel therapies to target the previously undruggable target protein PP2A. This funding will enable us to accelerate the development of our platform and advance the lead compounds towards clinical development."

The investment in Rappta follows recent Novo Seeds participation in Galecto's Series D and Chromologics seed financing rounds.

About Rappta Therapeutics

Rappta Therapeutics, based in Finland and the US, is developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). It has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A, a critical enzyme regulating protein de-phosphorylation and tumor growth, with the potential to create a new class of anti-cancer drugs. Rappta has a strong scientific, management and commercial team. Its scientific team, led by CSO and co-founder, Professor Goutham Narla, Head of Cancer Research at the University of Michigan, represent world-leading expertise in PP2A. It is backed by blue-chip investors Advent Life Sciences, Novartis Venture Fund, Novo Seeds and one family office. For more information, go to http://www.rappta-therapeutics.com.

About Novo Holdings A/S

Novo Holdings A/S is a private limited liability company wholly owned by the Novo Nordisk Foundation. It is the holding and investment company of the Novo Group, comprising Novo Nordisk A/S and Novozymes A/S, and is responsible for managing the Novo Nordisk Foundation's assets.

Novo Holdings is recognized as a leading international life science investor, with a focus on creating long-term value. As a life science investor, Novo Holdings provides seed and venture capital to development-stage companies and takes significant ownership positions in growth and well-established companies. Novo Holdings also manages a broad portfolio of diversified financial assets. Further information: http://www.novoholdings.dk

SOURCE Novo Holdings

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Novo Seeds co-leads Rappta Therapeutics Series A Financing for the Development of Phosphatase 2A drugs - PRNewswire

In a time already full of challenges and changes, some pregnant and postpartum women will also experience a rare but dangerous heart complication: an aortic dissection.

For a new investigation published in JAMA Cardiology, researchers studied the experiences of 29 participants in an international registry who were unexpectedly hospitalized for a dissection while pregnant. Most already had an underlying heart condition, although it was often not yet diagnosed.

SEE ALSO:Growth of Cardio-Obstetrics Care Presents Challenges, Opportunity

Aortic dissections only affect 3 in 100,000 people per year. They cause the layers of the aorta to tear, and blood to pool or leak instead of flowing normally. A patient needs a timely diagnosis and then urgent, life-saving medical attention.

Aortic diseases and conditions like Marfan syndrome or Loeys-Dietz syndrome are usually culprits in women who have a dissection while pregnant, the researchers say, although an association to high blood pressure, the most common risk factor in the general population, may exist, too.

Notably, the researchers found 19% of aortic dissections in women younger than 35 years old were associated with pregnancy. That means a woman already predisposed to have a dissection is more likely to have one during pregnancy, possibly due to hormones and changes to the body during pregnancy and postpartum.

Women in the cohort experienced dissections in all three trimesters of pregnancy in addition to within three months postpartum, although more cases occurred in the latter part of pregnancy and immediately following.

All of the participants who had a Type A aortic dissection, the most dangerous, underwent surgery to repair the dissection. Eighty-five percent of those women with a Type A dissection went into their pregnancies with a known diagnosis such as Marfan syndrome (the most common).

The participants who had a type B dissection were more likely to be given medication, although some received an open or minimally invasive heart surgery.

Given that aortic dissection is already rare, the ability to study a cohort of people who had the condition while pregnant provides an important opportunity, says senior author Kim Eagle, M.D., a director of the Michigan Medicine Frankel Cardiovascular Center and a professor of internal medicine.

Its important to understand what these women experienced, including their risk factors, underlying medical conditions and ultimate outcomes, in order to learn how best to care for others and to prevent future aortic dissections in this population, he says. Eagle started the International Registry of Acute Aortic Dissection, housed at Michigan Medicine, in 1996. Members include 57 active centers in 13 countries.

SEE ALSO:Registry Helps Move Aortic Dissection Care Forward

Twenty-eight of the 29 patients in the IRAD registry who had a dissection during pregnancy survived the hospitalization. The dissections studied in this publication occurred between 1998 and 2018 and the 29 women represent 1% of all women in the registry.

This is the 100th publication to come out of IRAD.

Twenty years ago, the seminal IRAD paper was published, aptly also in JAMA, detailing the first 454 patients, Eagle says. Over 10,000 patients and 24 years since data collection began, IRAD continues to influence our understanding and treatment of acute aortic dissection.

IRAD has been instrumental in characterizing the presentation of aortic dissection, along with better understanding its natural history and the impacts of different therapeutic approaches in the treatment of this very deadly disease, says Himanshu Patel, M.D., a cardiac surgeon and professor at Michigan Medicine. Patel leads adult cardiac surgery at the Frankel CVC, and co-leads the international cohort in IRAD.

Although aortic dissection is most often seen in older men, this cohort study underscores the importance of careful monitoring of cardiac conditions during pregnancy, researchers say.

Co-author Melinda Davis, M.D., part of the Cardio-Obstetrics team at Michigan Medicine with appointments in both cardiology and obstetrics and gynecology, says pre-pregnancy care for a woman with known aortic disease would include evaluation of maternal and fetal risk, counseling and possible genetic testing, followed by ongoing monitoring and testing.

IRAD is supported by R.L. Gore, Inc., the Ann and Bob Aikens Aortic Fund and The Tom Varbedian Fund for Aortic Research as well as grants from numerous participating IRAD aortic centers of excellence.

Paper cited: Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection. JAMA Cardiology. DOI: 10.1001/jamacardio.2020.4876.

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Tied to Undiagnosed Aortic Disease, Aortic Dissection in Pregnancy Proves Difficult to Predict - Michigan Medicine