Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D (LGMD2D)

Abstract (Word Count 280) In a previous LGMD2D clinical trial, robust alpha-sarcoglycan (αSG) gene expression was confirmed following intramuscular gene (SGCA) transfer. This paved the way for first in-human isolated limb infusion (ILI) gene transfer trial to the lower limbs. Delivery of scAAVrh74.tMCK.hSGCA via an intravascular route through the femoral artery predicted improved ambulation. This method was initially chosen to avoid safety concerns required for large systemic vascular delivery viral loads. We adopted ILI methods from the extensive chemotherapy experience for treatment of malignancies confined to the extremity. Six LGMD2D subjects were enrolled in a dose-ascending open-label clinical trial. Safety of the procedure was initially assessed in a single limb of a non-ambulant affected adult at the dose of 1x1012 vg/kg. Subsequently ambulatory children (ages 8-13) were enrolled and dosed bilaterally with either 1x1012 vg/kg per limb or 3x1012 vg/kg per limb. The 6-minute-walk-test (6MWT) served ...