📋 Tender Overview
Next-Generation Models And Genetic Therapies For Rare Neuromuscular Diseases
Muscle-On-A-Chip To Develop Gene Therapies For Neuromuscular Diseasemuscular Dystrophies, Such As Duchenne Muscular Dystrophy, Are Severe Genetic Disorders Causing Muscle Wasting, Immobility, And Early Death. Despite The Promise Of Gene Therapies And Genome Editing, Only One Product Has Recently Been Approved For One Form Of Muscular Dystrophy, Mainly Due To Lack Of Reliable Disease Models. The Eu-Funded Magic Project Aims To Overcome This Limitation By Creating Advanced Human Muscle Models Using Microfabrication And Stem Cells. These Muscle-On-A-Chip Devices Will Test New Viral Vectors And Gene Editing Tools For Safe And Effective Therapeutic Strategies. Researchers Aim To Develop Refined Vectors That Offer Precise Gene Expression And Limited Immune Responses, Which Can Be Further Validated In Large Animal Models Before Clinical Testing.
Funded Under
Health
Total Cost
€ 6 003 926,25
Eu Contribution
€ 6 003 926,25
Coordinated By
Institut National De La Sante Et De La Recherche Medicale
France
Objective
Muscular dystrophies are severe genetic disorders characterised by muscle wasting, impaired mobility and premature death, which to date remain incurable. Although preclinical and clinical evidence position genetic therapies amongst the key emerging treatments for several genetic conditions, no gene therapy or genome editing strategy has been approved for any muscular dystrophies yet. The lack of robust, human(ised) models enabling precise development of such advanced therapies is a major barrier towards their clinical translation for muscle diseases. To overcome this limitation, we have assembled the multidisciplinary MAGIC consortium to build novel, high-fidelity, models of human skeletal muscle pathophysiology which will be used to develop new vectors for safe and efficacious neuromuscular gene therapy and genome editing. Specific rare (paediatric) diseases targeted by our consortium are Duchenne muscular dystrophy (DMD), X-linked centronuclear myopathy (XLCNM), LMNA- and COL6-related congenital muscular dystrophies (CMDs). Microfabrication, microfluidics and human stem cell differentiation technologies will be used to generate disease-specific muscle-on-chip devices qualified for commercialisation, capable of screening toxicity and cell-specificity of new adeno-associated viral vector (AAV) capsid variants, and unique muscle-specific lentiviruses. Selected vectors will be equipped with novel lineage-specific regulatory elements to further restrict transgene expression to myofibres, muscle stem cells or interstitial fibroblasts, reducing also potential immunogenicity. The same vectors will be loaded with therapeutic genes or with new mutationindependent (for DMD and XLCNM) or mutation-specific (for LMNA- and COL6-CMD) gene editing tools, which will then be validated in dystrophic rodents. Finally, GMP-compatible batches of the top performing vectors will
