A study sponsored by Sarepta Therapeutics investigated the safety and efficacy of SRP-9005 (rAAVrh74 vector), one of their gene therapy products, when injected intravenously into the mouse model of GIST-related limb-girdle muscular dystrophy (LGMD R5).
Twelve weeks after administration of a minimum dose of 4.63 x 1012 vg/kg, the analyses show :
- good tolerance of the product ;
- successful delivery of the transgene to the targeted muscle tissues (limb muscles, diaphragm, heart)
- a significant decrease in the level of CPK in the blood;
- Restoration of gammasarcoglycan protein and improvement of muscle histopathology (reduction of fibrosis, normalisation of fibres, etc.);
- a functional improvement of the muscle, in particular a better ambulation.
These results are more robust at the highest dose (7.41 x 1013 vg/kg). They complete the data already acquired on the feasibility of gene therapy in this disease and allow the establishment of a minimum effective dose of SRP-9005 for future clinical trials.
