Gene therapy shows encouraging results in humans for limb-girdle muscular dystrophy linked to SGCB

An ongoing clinical trial sponsored by Sarepta Therapeutics is investigating the safety and efficacy of SRP-9003 (rAAVrh74. MHCK7.hSGCB vector) following systemic infusion in six patients with SGCB-related limb-girdle muscular dystrophy (LGMD R4).

Two years after administration of a minimum dose of 1.85 x 1013 vg/kg, analyses showed :

  • the product was fairly well tolerated, with two cases of serious adverse events (hepatitis and severe dehydration due to vomiting) which were resolved and did not result in discontinuation of the clinical trial;
  • Successful transduction (greater at higher doses), with robust expression of full-length SGCB protein in skeletal muscle;
  • a mean reduction in blood CPK levels of between 67 and 83%;
  • restoration of beta-sarcoglycan protein to between 54% and 60% of normal, and restoration of the sarcoglycan complex in the sarcolemma;
  • an improvement in muscle function, with average increases of 0.5 to nearly 6 points on the NSAD score, while the control group showed a drop in the average score over the same period.

These positive results have prompted Sarepta Therapeutics to begin preparations for a phase 3 trial (EMERGENE), for which recruitment (15 patients aged four and over, walking or not) is currently underway.


Gene therapy with bidridistrogene xeboparvovec for limb-girdle muscular dystrophy type 2E/R4: phase 1/2 trial results. Mendell, J. R., Pozsgai, E. R., Lewis, S. et al. Nat Med 2024.


Sarepta Therapeutics Initiates Screening in EMERGENE, a Phase 3 Clinical Study of SRP-9003 for the Treatment of Limb-Girdle Muscular Dystrophy Type 2E/R4. Communiqué de presse 2024 Sarepta Therapeutics.