Congenital Structural Myopathy

NEW YORK--( BUSINESS WIRE )-- RTW Charitable Foundation (“RTWCF”) announced today that it has awarded $900,000 in research grants to support six research studies. These studies aim to drive transformational progress in genetic therapies and align with RTWCF’s mission to power community initiatives and scientific research to improve the health of underserved communities. Grant Recipients The following studies and researchers each received $150,000 research grants from RTWCF: “ Establishing gene replacement therapy for NEDAMSS, an ultra-rare neurological disorder caused by mutations in the IRF2BPL gene” (Kathrin Meyer, Nationwide Children’s Hospital, Columbus, OH). “ Optimizing AAV-SPL gene therapy for sphingosine phosphate lyase insufficiency syndrome” (Julie Saba, University of California, San Francisco, San Francisco, CA). “Gene therapy for SURF1-related Leigh Syndrome” (Steven Gray, The University of Texas Southwestern, Dallas, TX). “ Safety and toxicity assessment of AAV-based gene therapy for creatine transporter deficiency” (Jagdeep Walia, Queen’s University, Kingston, Ontario, Canada). “Advanced therapeutics for SELENON-related myopathy” (Alan Beggs, Boston Children’s Hospital, Boston, MA). “ Preclinical studies of ASO therapy for SPTLC1-related hereditary sensory neuropathy” (Haiyan Zhou, University College London, London, UK). “ Despite considerable advancements in gene and cell therapies that deliver more targeted and effective treatments for rare diseases, a significant amount of additional research is still required to move these advances out of the lab and safely to patients,” said Juan Carlos López, PhD, Managing Director, Research Grants, RTW Charitable Foundation. “ RTW Charitable Foundation is proud to provide financial and scientific support to these six incredible researchers and their respective studies. We believe that each of these studies will help expedite the development of gene therapies for rare and ultrarare diseases, and greatly improve the lives of individuals with unmet medical needs.” Grant Recipient Commentary Julie Saba, MD, PhD, commented : “ I am honored and grateful to receive this award from RTWCF, which will support studies to optimize gene therapy for sphingosine phosphate lyase insufficiency syndrome. This newly recognized inborn error of metabolism leads to kidney failure in most of the affected children, causing more than half of them to die in their first years of life. While kidney transplantation can be lifesaving, it is invasive, costly, unavailable to many, and does not address the many other serious consequences of the disorder. Gene therapy offers a potentially lifesaving alternative treatment. The studies undertaken with RTWCF funding should improve our gene therapy potency, allowing us to advance to toxicology studies and clinical trials. I appreciate RTWCF’s dedication to advancing research in ultrarare diseases, which are overwhelmingly underfunded. Every child deserves personalized therapy!” Alan Beggs, PhD, commented: “ Our group has studied a neuromuscular condition called Multiminicore Disease or Rigid Spine Muscular Dystrophy for many years to understand how mutations of a gene called SELENON lead to weakness. We are now on the cusp of translating our laboratory experiments into a treatment that can be tested in patients. I’m thrilled that support from the RTWCF is helping us to work towards developing a next-generation gene therapy candidate designed for eventual testing in a clinical trial.” Haiyan Zhou, MD, PhD, commented: “ We are extremely grateful for the generous award from RTWCF. This grant serves as a vital catalyst in advancing our groundbreaking work on a novel nucleic acid therapy designed for an ultrarare neurodegenerative condition, currently devoid of effective treatment options. The crucial support from RTWCF will propel the preclinical development and hasten the clinical translation of this experimental therapy. Moreover, this award will play a pivotal role in elevating the impact of our translational genetic therapy program at the Great Ormond Street Institute of Child Health and NIHR GOSH Biomedical Research Centre. It also contributes to the growth of the UK platform for nucleic acid therapy in rare diseases.” To date, RTWCF has awarded over 20 research grants, totaling over $3 million in funding. In addition to delivering financial resources, RTWCF also provides grant recipients with hands-on scientific support, helping them improve or further develop their research and research tools and identify new therapeutic targets. About RTW Charitable Foundation Founded in 2018 as the charitable foundation arm of RTW Investments, LP, RTW Charitable Foundation works to power community initiatives and scientific research to improve the health of underserved communities. The Foundation is able to provide capital, manpower, and logistical support to help scientists push such projects forward. In addition, the Foundation aims to assist in advocacy, disease awareness and directly support organizations and communities in New York City. To learn more, visit www.rtwcf.org .

ARMGO Pharma Publishes Positive Phase 1b Trial Results of Rycal® ARM210 for the Treatment of Ryanodine Receptor 1 Related Myopathies Phase 1b open label trial confirms safety and tolerability of 120 mg and 200 mg dosing of ARM210 daily in patients with Ryanodine Receptor 1 Related Myopathies Provides first signs of clinical efficacy improving fatigue and proximal muscle strength in patients at 200 mg daily Corroborates allosteric mechanism of action of Rycal® ARM210 to restore muscle function by repairing mutated ‘leaky’ Ryanodine Receptor 1 channels January 29, 2024 – ARMGO Pharma, Inc. (ARMGO), a clinical stage biopharmaceutical company advancing a novel class of small molecule drugs known as Rycals®, announced today the publication of the results from a Phase 1b study of its Rycal ARM210 (also known as S48168), for the treatment of Ryanodine Receptor 1 Related Myopathies (RYR1-RM), an orphan muscle disease. The data was published in a paper entitled ‘Rycal S48168 (ARM210) for RYR1-related myopathies: A phase one, open-label, dose-escalation trial’ authored by Dr Joshua Todd et al in the peer reviewed Journal eClinicalMedicine, part of the Lancet family of publications. The paper reviews data from the Phase 1b study of ARM210 and its novel allosteric mechanism of action (MoA) targeting the root cause of RYR1-RM: mutated Ryanodine Receptor 1 (RYR1). The RYR1 gene encodes RyR1, an intracellular calcium-release channel that becomes leaky in muscle diseases. Intracellular calcium leaks caused by mutant RyR1 channels impair muscle contraction leading to muscle weakness and loss of function, and activate toxic pathways that damage muscle, causing the symptoms in RYR1-RM. The Phase 1b, open-label, dose-escalation trial confirmed safety, tolerability and pharmacokinetics of 120 and 200 mg dosing of ARM210 daily over for 29 days in adult men and women affected with RYR1-RM. Importantly, it also demonstrated preliminary efficacy in the higher dose group in two hallmark symptoms of RYR1-RM: 1) significant alleviation of fatigue assessed by PROMIS-fatigue t-scores and 2) improved proximal muscle strength assessed by physical shoulder abduction exam (Medical Research Council grading). These results warrant further development of ARM210 as a potential disease modifying treatment for RYR1-RM in a randomized, placebo-controlled Phase 2 trial. The completed Phase 1b trial was conducted in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) under a Cooperative Research and Development Agreement (CRADA), with the support of the RYR-1 Foundation, Pittsburgh, PA, USA. “We are very pleased with the results of the RYR1-RM trial conducted together with the NIH, as the study has confirmed the safety and tolerability of ARM210, but most importantly, it has demonstrated for the first time that our Rycal®, ARM210, can reverse symptoms of this devastating, chronic muscle disease in a short treatment period. That is very promising”, said Gene Marcantonio, M.D., Ph.D., Chief Executive Officer of ARMGO Pharma. “We look forward, therefore, to rapidly continuing the development of ARM210 to bring this potential first treatment to RYR1-RM patients with the support of the RYR-1 Foundation and the patient community.” Michael F. Goldberg, M.D., M.P.H., Co-Chair of Research of the RYR-1 Foundation added, “We are elated by the publication of this important study, as it represents a beacon of hope for the many individuals and families from around the world who are affected by RYR1-RM. We look forward to the next stages in the development of this important drug.” Further information about this Phase 1b trial can be found online at: https://clinicaltrials.gov/study/NCT04141670. The trial was supported by Intramural Research Programs of the NIH/NINDS, NIH/NINR, a NIH Clinical Center Bench to Bedside Award (2017-551673) and ARMGO’s previous collaboration partner Les Laboratoires Servier. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publication reference: Rycal S48168 (ARM210) for RYR1-related myopathies: a phase one, open-label, dose-escalation trial, Todd et al, eClinicalMedicine https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00012-9/fulltext ARM210 (S48168) is a small molecule of the Rycal class, owned and developed by ARMGO for the treatment of Ryanodine Receptor mediated diseases such as RYR1-RM. It is an allosteric modulator that binds preferentially to leaky RyR channels and repairs the leak, as previously demonstrated in vitro in muscle biopsies from RYR1-RM patients. ARM210 (S48168) is currently undergoing Phase 2 clinical development for a second orphan indication, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a genetic arrhythmia caused by mutations in RYR2, the cardiac calcium channel gene. ARM210 (S48168) was awarded orphan drug designation for RYR1-RM in 2018 by the FDA and for CPVT in 2020. ARMGO also has a rare pediatric disease designation for CPVT. ARMGO Pharma, Inc., is a privately held biopharmaceutical company dedicated to developing novel small-molecule therapeutics to treat cardiac, and musculoskeletal disorders characterized by leaky Ryanodine Receptor (RyR) calcium channels. The Company’s proprietary drugs, known as Rycals®, are a new class of oral agents that repair these leaky calcium channels. ARM210, ARMGO’s most advanced Rycal, is currently in clinical development for two rare and orphan diseases, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a life-threatening cardiac disease and RYR1-Related Myopathy (RYR1-RM) a severe muscle disease. ARMGO Pharma has an exclusive, worldwide license from Columbia University for its RyR technology based on the research of founding scientist Andrew R. Marks, M.D. The Pittsburgh, Pennsylvania-based 501(c)(3) public charity was launched in October 2014. It is currently the only organization that exists solely to advocate for and serve the needs of individuals affected by RYR-1-related diseases (RYR-1-RD), the most common cause of congenital myopathy. The RYR-1 Foundation supports research leading to an effective treatment or a cure for RYR-1-RD. To achieve this mission, The RYR-1 Foundation has several goals: 1) Support Research: The RYR-1 Foundation makes grants to researchers interested in RYR-1-RD. Developing a patient registry is also key to promoting clinical trials of potential therapies. 2) Medical Professional Education: The vast majority of medical professionals have never heard of RYR-1-RD. The RYR-1 Foundation raises awareness through resources on our website, including the latest medical literature, as well as direct meetings with medical professionals around the world. 3) Patient/Family Support and Advocacy: Due to the rarity of RYR-1-RD, receiving this diagnosis can be an anxiety-provoking and isolating experience for an affected patient and their families. The RYR-1 Foundation serves as a resource for patients and their families through our website, other forms of social media, and family conferences. The content above comes from the network. if any infringement, please contact us to modify.

HONG KONG, Jan. 10, 2024 /PRNewswire/ -- The Centre for Chinese Herbal Medicine Drug Development of Hong Kong Baptist University (HKBU) has developed a new drug using effective components of a Chinese herbal medicine, Chaenomelis Fructus, for the treatment of the rare disease, myofibrillar myopathy. The drug has obtained the orphan drug designation from the US Food and Drug Administration (FDA), and is the first botanical drug in Hong Kong to receive this qualification. Continue Reading Professor Bian Zhaoxiang, Associate Vice-President (Chinese Medicine Development) and Director of the Centre for Chinese Herbal Medicine Drug Development at HKBU (2nd right); Dr Lin Chengyuan, Assistant Director (Administration) (2nd left); Dr Hou Mengyang, Postdoctoral Research Fellow (1st right); and Mr Duan Zhigang, Senior Regulatory Affairs Manager (1st left) of the Centre introduce the new drug for the treatment of myofibrillar myopathy. Success in obtaining orphan drug (a drug used for treating rare disease) designation will accelerate the approval process of the new drug, including speeding up of the review process, waiver of the marketing authorisation fee, and seven years of market exclusivity for the approved product. The research team plans to submit an Investigational New Drug application to FDA in two years to conduct clinical trials. Lack of effective treatment for myofibrillar myopathy Myofibrillar myopathy, primarily caused by genetic mutations, including the BAG3 gene, is a rare hereditary neuromuscular disorder with symptoms resembling muscular dystrophy. It typically manifests during adolescence and is characterised by severe clinical symptoms, including progressive muscle weakness, muscle atrophy, motor impairment, muscle stiffness, respiratory muscle involvement, and cardiomyopathy. Currently, there is no effective treatment for myofibrillar myopathy, and the high cost of treatment poses significant burdens for patients, their families and society. Due to the rarity of this disease, researchers are still exploring the treatment approaches for this disease and evaluating their safety and efficacy. Focusing on myofibrillar myopathy caused by BAG3 gene mutation (Bag3opathy), the Centre for Chinese Herbal Medicine Drug Development made reference to clinical cases, integrated Chinese medicine theory with modern scientific technology, and made use of the effective components of a Chinese herbal medicine Chaenomelis Fructus to develop a new drug named CDD-2107. New drug with effective components of Chaenomelis Fructus The commonly used Chinese herbal medicine Chaenomelis Fructus is the dried mature fruit of Chaenomeles speciosa (Sweet) Nakai, which belongs to the Rosaceae family. It is widely used for joint and muscle disorders, such as paralysis caused by summer heat-dampness, and pain in the waist and knee joints. Though bearing very similar Chinese names, Chaenomeles speciosa is different from the fruit papaya belonging to the Carica genus of the Caricaceae family. The research team, based on traditional Chinese medicine theory with a focus on clinical efficacy, applied modern Chinese medicine extraction and purification techniques in their studies. They identified the most important and effective components from the patients' Chinese medicine prescriptions, and uncovered through research the potential treatment mechanism of CDD-2107, which could significantly relieve clinical symptoms in patients with myofibrillar myopathy by enhancing muscle strength, improving mobility, and increasing independence, thus offering new hope to the patients. First local Chinese medicine drug granted US orphan drug designation Professor Bian Zhaoxiang, Associate Vice-President (Chinese Medicine Development) and Director of the Centre for Chinese Herbal Medicine Drug Development at HKBU, said: "CDD-2107 is the fruit of the integration of Chinese medicine theory and modern technology. Receiving the orphan drug designation by FDA for CDD-2107 is an encouraging milestone and recognition of our team's dedication to scientific innovation." The development and production of orphan drugs face many challenges, such as limited research data, high research and development costs, and small market size. Therefore, some countries or regions have implemented various policies and measures to encourage pharmaceutical companies to engage in research and production of drugs for the treatment of rare diseases. Once an orphan drug is approved by the FDA, the pharmaceutical organisations concerned may receive special incentives and support, such as research funding, extended patent protection, market exclusivity, and tax credits. Professor Bian concluded: "We plan to submit an Investigational New Drug application in two years, which will be a crucial milestone in establishing CDD-2107 as an internationally recognised, safe, and effective treatment for Bag3opathy. Our ultimate goal is to obtain FDA approval for selling CDD-2107, benefiting more patients." SOURCE Hong Kong Baptist University