Indexed on: 11 Aug '16Published on: 11 Aug '16Published in: Molecular Therapy
Duchenne muscular dystrophy (DMD) is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever dystrophic dogs (GRMD) represent the best pre-clinical model of DMD, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in GRMD. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected GRMD dogs. The occurrence of T-cell response in three GRMD dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin.