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FSHD Society Establishes Genetic Testing Program To Advance Clinical ...

TestFSHD overcomes barriers by streamlining FSHD genetic testing for clinicians and patients

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RANDOLPH, Mass., Oct. 18, 2022 /PRNewswire-PRWeb/ -- The FSHD Society has launched a direct-to-patient clinical diagnostic genetic testing program for facioscapulohumeral muscular dystrophy (FSHD). Called TestFSHD, the program's aim is to overcome critical barriers that patients currently face when trying to obtain genetic testing for the rare, debilitating muscle disorder. FSHD is one of the most common hereditary muscle diseases and is thought to affect nearly one million individuals world-wide. Because of widespread lack of access to diagnostic testing, the majority of those who have FSHD have not had their diagnosis confirmed genetically.

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The TestFSHD program ensures that eligible U.S.-based patients seeking a clinically approved genetic diagnosis of FSHD have a comprehensive and streamlined path to a genetic test. The program provides virtual genetic counseling, medical referrals, mobile blood-draws, and comprehensive FSHD1 and FSHD2 genetic testing. These services are provided by Genome Medical, a telemedicine company specializing in genetic counseling, with blood-draws by ExamOne phlebotomy service and genetic tests requisitioned from commercial diagnostic laboratories such as PerkinElmer Genomics and the University of Iowa Diagnostic Laboratories. Genome Medical counselors can also assist patients in filing claims with their health insurance.

"Confirmation of FSHD by a clinically approved genetic test remains one of the primary barriers impacting rapid recruitment into clinical trials," explains Jamshid Arjomand, PhD, Chief Science Officer at the FSHD Society. "The TestFSHD program provides patients with a solution to overcome barriers to clinical trial eligibility, which should help streamline the recruitment process in upcoming trials."

The lack of access to genetic testing had become an obstacle to progress because many treatments being developed for FSHD target the genetic cause of the condition. This means that patients must be genetically confirmed to have FSHD before they can enroll in clinical trials or, eventually, be eligible to receive such treatments. The Society noted that the low percentage of patients with genetically confirmed FSHD could undermine or slow down upcoming clinical trials. To build up a 'trial-ready' patient population, the FSHD Society analyzed the obstacles faced by patients, identified the partner companies to provide solutions, and established a process so each part of the system connected smoothly to the others.

The program has clearly had its intended impact. "I was diagnosed with FSHD over 11 years ago," said one individual. "I recently completed the free genetic testing that you offered, and I met with the genetic counselor yesterday…I came back with a positive blood test [for] FSHD Type 1. I am ready and willing to take part in any clinical trials as soon as I'm able."

The FSHD Society partnered with Arrowhead Pharmaceuticals, Avidity Biosciences, Dyne Therapeutics, Fulcrum Therapeutics and Pfizer to sponsor a pilot of TestFSHD, which made the testing free for the first 150 qualifying patients. "These partnerships demonstrate the enthusiasm of key stakeholders to collectively advance a trial-ready patient community in collaboration with the FSHD Society," remarks Ken Khatava, Chief Growth Officer at the FSHD Society.

The sponsored, free phase of the program will end on October 31, 2022, but TestFSHD will remain in place to make it easy for patients and families to obtain clinical genetic testing, with the cost reimbursed by their health insurance or covered out of pocket. "The extreme difficulty of getting genetic testing for FSHD has long been a pain point in the patient journey," explains Arjomand. "We are thrilled that TestFSHD empowers patients to obtain affordable genetic testing for themselves."

To learn more, visit fshdsociety.Org/testfshd

ABOUT THE FSHD SOCIETY The FSHD Society is the world's largest research-focused patient advocacy organization for facioscapulohumeral muscular dystrophy (FSHD), one of the most prevalent forms of muscular dystrophy. The Society has catalyzed major advancements and is accelerating the development of treatments and a cure to end the pain, disability, and suffering endured by one million people worldwide who live with FSHD. The FSHD Society has transformed the landscape for FSHD research and is committed to making sure that no one faces this disease alone. The Society offers a community of support, news, and information through its website at fshdsociety.Org

Media Contact

June Kinoshita, FSHD Society, 781-301-6649, [email protected]

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SOURCE FSHD Society

Largest North American Site For FSHD Muscular Dystrophy Testing Adopts ...

University of Iowa to use Bionano-based assay to replace most "gold standard" Southern blot tests for molecular diagnosis of FSHD

SAN DIEGO, April 22, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that the University of Iowa Hospitals and Clinics (UIHC) will switch their method of clinical molecular testing for patients with presumed Facioscapulohumeral Muscular Dystrophy (FSHD) to optical mapping using Bionano's Saphyr System. The UIHC recently completed development of an FSHD assay on Saphyr and validated its results by processing patient samples for FSHD.  Following this evaluation, the UIHC is implementing this month a Saphyr-based assay into its clinical testing workflow.

FSHD affects approximately 1 in 10,000 individuals in the United States. It is usually caused by deletion or loss of DNA in a section of chromosome 4 shortening a critical repeat element, the D4Z4 repeat, that plays an essential role in regulating the expression of the DUX4 gene. One component of genetically confirming a diagnosis of FSHD is measuring the exact number of D4Z4 repeats.

The Molecular Pathology Laboratory at the University of Iowa, directed by Aaron Bossler MD, PhD, is the largest FSHD testing site in North America and to date has relied on the labor-intensive technique of Southern blotting for FSHD molecular diagnostic testing. The Saphyr System from Bionano provides a safe, fast and automated system to more accurately size patient alleles and determine the number of D4Z4 repeats. The University of Iowa FSHD testing involves a comprehensive algorithm which utilizes Bionano's EnFocus™ FSHD Analysis tool to accurately represent the repeat number with a high sensitivity for mosaicism and distinguish the presence or absence of the permissive haplotype for pathogenic and non-pathogenic variants.

Dr. Bossler commented: "The optical mapping technology and analysis program from Bionano is very useful for FSHD testing because the allele repeat sizing is highly accurate, the assay uses a lot less specimen and the turnaround time is faster. We anticipate that it will improve our ability to identify pathogenic alleles for this challenging disease."

While FSHD testing is the first assay to be developed and validated using the Saphyr platform, the UIHC molecular team is assessing other genetic targets to analyze with Saphyr in order to diagnose other disease-associated chromosomal abnormalities.

Erik Holmlin, PhD, CEO of Bionano Genomics commented: "Bionano Genomics continues to push into clinical settings and provide clinicians with a modern tool to re-evaluate and streamline the practice of molecular diagnostics and cytogenetics.  We are thrilled to see the team at the University of Iowa complete their validation and begin offering patients an accurate, next-generation assay based on our Saphyr system, which we expect will benefit clinicians, patients and their families.  We believe the FSHD assay will be the first in a wide array of clinical assays that the UIHC and other labs will develop with our technology."

About Bionano Genomics

Bionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing. Bionano's 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. For more information, visit www.Bionanogenomics.Com.

Forward-Looking Statements This 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, our expectation that the Saphyr-based FHSD assay will benefit clinicians, patients and their families, and our belief regarding the development of other clinical assays by the University of Iowa and other labs using our technology. 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 that Saphyr may not be as effective as expected and the UIHC could deemphasize its use of the Saphyr system, as well as risks and uncertainties associated with 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 key clinical studies to demonstrate the effectiveness of our products; the loss of key members of management and our commercial team; and the risks and uncertainties associated with our 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.

Contacts

Company Contact:Erik Holmlin, Ph.D., CEOBionano Genomics, Inc. +1 (858) 888-7600eholmlin@bionanogenomics.Com

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

Media Contact:Kirsten ThomasThe Ruth Group+1 (508) 280-6592kthomas@theruthgroup.Com   

Department of Pathology:Aaron Bossler, MD, PhDDirector, UIHC Molecular Pathology(319) 384-9566aaron-bossler@uiowa.Edu

Robert A. Robinson, MD, PhDMedical Director, UIDL319-356-4163Robert-a-robinson@uiowa.Edu

UIDL Business Relations: Mary Sue OtisManager, UIDL319-356-3533Marysue-otis@uiowa.Edu

UIDL Client Services for shipping and ordering questions and supplies:866-844-2522UIDLClientServices@healthcare.Uiowa.Edu 

Source: Bionano Genomics

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

Mutations In Genes That Modify DNA Packaging Result In ...

A recent finding by medical geneticists sheds new light on how Facioscapulohumeral Muscular Dystrophy develops and how it might be treated. More commonly known as FSHD, the devastating disease affects both men and women.

FSHD is usually an inherited genetic disorder, yet sometimes appears spontaneously via new mutations in individuals with no family history of the condition.

"People with the condition experience progressive muscle weakness and about 1 in 5 require wheelchair assistance by age 40," said Dr. Daniel G. Miller, University of Washington associate professor of pediatrics in the Division of Genetic Medicine. Miller and his worldwide collaborators study the molecular events leading to symptoms of FSHD in the hopes of designing therapies to prevent the emergence of symptoms or reduce their severity.

In the Nov. 11 online issue of Nature Genetics, Miller and Dr. Silvere M. Van der Maarel of Leiden University in The Netherlands, along with an international team, report their latest findings on the role of epigenetic modifications in causing the disease. In Seattle, Dr. Stephen Tapscott of the Fred Hutchinson Cancer Research Center was also a major contributor to the project. He is a UW professor of neurology and a researcher at the UW Center for Human Development and Disability.

Epigenetics refers to mechanisms that influence how the genome is regulated and how, where and when genes act -- all without altering the underlying DNA sequence. The flexibility of DNA packaging -- its wrapping, which can be tightened and loosened, and its chemical tags -- is one of the epigenetic forces on the genome. This packaging is called the chromatin structure and is one way specialized cells such as those in our muscles allow groups of genes to be shut off, or be available for expression.

Patients with FSHD, usually have a deletion of genetic material that reduces the number of copies of a repeated DNA sequence arrayed on chromosome 4. The deletion alters the chromatin structure of the region and allows the muscle-toxic DUX4 genes within each repeat to be inappropriately activated.

"Most genetic mutations reduce the production of a protein, or a mutated gene might produce a detrimental protein," Miller said. "FSHD is unusual because it is most often caused by genetic deletions that paradoxically result in the production of DUX4 in the wrong tissue at the wrong time. "

Scientists have previously shown that the genetic deletions in FSHD somehow caused an epigenetic change -- an alteration in one of the mechanisms that control a gene's activity. The relaxation of the tightly wound chromatin structure allowed the otherwise sealed code in the gene to be read and the toxic DUX4 to be produced in skeletal muscle.

"Our study builds on this model and identifies a new mechanism that allows this relaxation and DUX4 production to occur. Production of DUX4 in muscle cells can be viewed as a molecular switch. We've discovered that the switch that turns on DUX4 expression can be activated in different ways but the mechanism of muscle destruction by DUX4 remains the same. Identifying different ways the switch can be activated is a crucial step toward therapy development because it allows us to apply multiple and different strategies to prevent activation of the switch." Miller said.

Five percent of FSHD-affected individuals have array lengths, longer than 10 copies (the threshold for chromatin relaxation) of the DNA sequence in question making them appear to lack the genetic mutation that normally causes FSHD.

However, these unusual individuals lacked repression of DUX4 code-reading in their skeletal muscle cells because of a mechanism other than copy number.

"Breakthroughs in scientific discovery are often achieved by studying individuals with unusual disease presentations," Miller said. The researchers identified individuals without the usual FSHD-disease causing DNA deletion but who still lacked repression of the DUX4 code reading.

Dr. Rabi Tawil at the University of Rochester made the clinical diagnosis in these people and established cultures of muscle cells from biopsies. Dr. Richard Lemmers working in van der Maarel's laboratory demonstrated that the chromatin structure was relaxed despite a normal number of repeat units on chromosome 4. With the help of Dr. Michael Bamshad, UW professor of pediatrics, and Dr. Deborah Nickerson, UW professor of genome sciences, Miller and his group sequenced and analyzed the protein coding portions of the genomes of individuals with FSHD caused by this uncommon mechanism.

The researchers discovered that these individuals had causative mutations in the Structural Maintenance of Chromosomes Hinge Domain 1 gene. Mutations in this gene cause decreased levels of the SMCHD1 protein and result in relaxation of the chromatin structure surrounding the muscle cells' DNA allowing toxic DUX4 to be generated.

"The discovery linking mutations in the SMCHD1 gene with FSHD is particularly satisfying," Miller said, 'because the normal form of SMCHD1 has an established role in repressing the reading of portions of the DNA code. SMCHD1 Is involved in silencing one of the two X chromosomes in females and in turning off repetitive elements in other parts of the genome.

Understanding the FSHD-causing mechanism of SMCHD1 mutations, Miller said, suggests ideas for therapeutic strategies to suppress the production of the muscle-damaging DUX4 and for treatments for the more common forms of FSHD.

This work was supported by grants from the NIH (NINDS P01NS069539; CTSA UL1RR024160; NIAMS R01AR045203; NHGRI HG005608 and HG006493), NGI Horizon Valorization Project Grant (Nr 93515504), The University of Washington Center for Mendelian Genomics (1U54HG006493), the MDA (217596), the Geraldi Norton and Eklund family foundation, the FSH Society, The Friends of FSH Research, EU FP7 framework program agreements 223026 (NMD-chip) and 223143 (TechGene), and the Stichting FSHD.

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