Author:

Keywords:

Duchenne Muscular-Dystrophy, Skeletal-Muscle, Gene-Therapy, T-Cells, Expression, Multipotent, Repair, Transplantation, Population, Delivery, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, DUCHENNE MUSCULAR-DYSTROPHY, SKELETAL-MUSCLE, T-CELLS, EXPRESSION, MULTIPOTENT, THERAPY, REPAIR, TRANSPLANTATION, POPULATION, DELIVERY, Adult Stem Cells, Animals, Combined Modality Therapy, Creatine Kinase, Dogs, Dystrophin, Genetic Therapy, Humans, Male, Muscle Cells, Muscular Dystrophy, Animal, Muscular Dystrophy, Duchenne, Recombinant Fusion Proteins, Stem Cell Transplantation, Transplantation, Autologous, Transplantation, Heterologous, General Science & Technology

Abstract:

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function ( confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.