The calpainopathy or LGMDR1 (previous nomenclature LGMD2A) is a form of Limb Girdle Muscular Dystrophies.
This disease is caused by mutations in the calpain 3 gene that lead to degeneration of the muscular cells (ORPHA:267)
This rare disease is the most frequent LGMD in the world. It is characterized by progressive weakness of the trunc and upper thigh muscles, usually beginning between 8 and 15 years old, with a loss of ambulation occurring 10 to 20 years later.
Genethon has been a pioneer in this domain, from the identification of the gene responsible for the disease to the first gene transfer tools. Several studies demonstrating the efficacy of the gene therapy approach against calpainopathy were published by its team.
- Bartoli, M., Bourg, N., Stockholm, D., Raynaud, F., Delevaque, A., Han, Y., Borel, P., Seddik, K., Armande, N. and Richard, I.: « A mice model for monitoring calpain activity in physiological and pathological conditions ». J Biol Chem 281 (2006) 39672-80.
- Bartoli, M., Roudaut, C., Martin, S., Fougerousse, F., Suel, L., Poupiot, J., Gicquel, E., Noulet, F., Danos, O. and Richard, I.: « Safety and Efficacy of AAV-Mediated Calpain 3 Gene Transfer in a Mouse Model of Limb-Girdle Muscular Dystrophy Type 2A ». Mol Ther 13 (2006) 250-259.
- Roudaut, C., F. Le Roy, et al. (2013). « Restriction of Calpain3 Expression to the Skeletal Muscle Prevents Cardiac Toxicity and Corrects Pathology in a Murine Model of Limb-Girdle Muscular Dystrophy. » Circulation.
Between 2004 and 2006, Genethon coordinated a natural history study on 85 patients from 3 sites (Paris, Saint Pierre – Ile de la Réunion, France and San Sebastian, Spain) in order to better know the disease and facilitate the design of the future clinical studies.
These results were published in 2016: Richard, I., et al. (2016). « Natural history of LGMD2A for delineating outcome measures in clinical trials. » Ann Clin Transl Neurol 3(4): 248-265.
This currently preclinical stage program aims at bringing a sufficient amount of therapeutic protein in patient muscles while assuring an absence of deleterious effect.