LGMD2D or alpha-sarcoglycanopathy is an ultra-rare, severe, debilitating condition characterized by progressive muscle fibers loss, inflammation, and muscle fiber replacement with fat and fibrotic scars. Learn more about LGMD2D.
The goal of gene therapy for LGMD2D is to permanently enable the muscle cells to produce the critical alpha-sarcoglycan protein, after intravenous administration of a vector containing the alpha-sarcoglycan gene and a promoter that only turns on the gene in muscle cells. Establishing alpha-sarcoglycan production in the muscle cells is expected to result in significant improvement in symptoms, with greater improvement toward normal ambulatory independence, the earlier in the disease the treatment is administered, and with the potential to prevent any symptoms of the disease from occurring when administered to newborns with confirmed LGMD2D from genetic testing.
Research to date:
Studies of treatment with the gene therapy in the lab of L. Rodino-Klapac at Nationwide Children’s Hospital, in a 4-5 week old alpha-sarcoglycan deficient mouse model, resulted in muscle cells maintaining force comparable to healthy normal mice after treatment with the gene therapy. Physical activity and a marker of muscle damage (creatine kinase (CK)) were also maintained at near normal healthy levels, despite both being significantly adversely affected in untreated alpha-sarcoglycan deficient mice. LGMD2D patients dosed with the proposed gene therapy by direct intramuscular injection, or via intravascular delivery to isolated lower limbs showed expression of the alpha-sarcoglycan protein in muscle fibers exposed to the gene therapy.
In late 2018, MYO-102 received Orphan Drug Designation from the U.S. Food and Drug Administration. A systemic i.v. dosing clinical trial is expected to begin in early 2020.