Advanced therapies for high burden skeletal muscle pathologies
Description: Skeletal muscle is a critical target organ to treat or prevent a large variety of disorders, collectively belonging to Neuromuscular Disorders. With skeletal muscle being the largest tissue of our body (representing 30-40% of total body mass), neuromuscular disorders greatly impair quality of life and pose a heavy financial burden to the European health care system. In addition, skeletal muscle atrophy is a hallmark of aging and cancer-related afflictions, leading to muscle weakness and increased risk of falls and hospitalization. Despite the high burden of these greatly prevalent pathologies, there is currently no definite therapy and clinical trial attempts have not provided positive results for the vast majority of them. We will develop advanced therapeutic interventions that will enhance muscle regenerative capacity, with the ultimate goal of prolonging health span as well as lifespan. We will investigate two mechanistically distinct genetic causes of muscle degeneration, Duchenne Muscular Dystrophy (DMD) and FacioscapuloHumeral Muscular Dystrophy (FSHD), as two major genetic causes leading to muscle wasting and degeneration without therapeutic options. The MuscleDARE consortium will unite academic and industrial partners to establish a personalized therapeutic platform and a proof-of-concept pipeline for genome editing gene therapy to treat these emblematic neuromuscular disorders. Our research program is organized along 3 interconnected axes: 1. Preclinical efficiency, specificity and safety evaluation: Proof-of-principle in large animal models for CRISPR/Cas9-based correction of muscle stem cells (MuSCs), development of viral and non-viral delivery systems, innovative multiparametric evaluation and complementary pharmaceutical improvement. --> Focus on MuSC targeting promises long-lasting persistence of strengthened myofibers and long-term therapeutic benefits, in contrast to common treatments that provide no lasting effects or cure. --> A major axis of our program will be immunogenicity considerations and safety evaluation to enhance the translational value of the developed advanced therapies. 2. Personalized therapeutics: Establish a therapeutic workflow that will translate in patient iPSC-based and organoid-based genome editing platform. Given the variety of mutations that underlie neuromuscular disorders, including DMD and FSHD, this personalized platform will help us expand the developed therapeutic benefit to virtually any patient. 3. Personalized medicine: Recruit patient cohorts, design state-of-the-art patient evaluation and care, and prepare for a clinical trial in strict compliance with regulatory requirements. In summary, the basic-to-clinical pipeline that will be established will provide personalized genome editing advanced therapeutics that can be used in a vast number of monogenic diseases afflicting a major part of the European population.
Funder: Agence Nationale de la Recherche
Amount: €29,680
Funding type: grant
Funder scheme: MRSEI
Start date: 2021-04-20
Investigator: Frédéric RELAIX
Institution: Institut Mondor de recherche biomédicale
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: ANR-21-MRS1-0005
OpenAlex ID: G3244217412