Cell Therapy of Duchenne Muscular Dystrophy by Intra-Arterial Delivery of HLA-Identical Allogeneic Mesoangioblasts

Stem cell therapy is a promising approach to correct genetic diseases that currentl lack an efficacious therapy, among which Duchenne Muscular Dystrophy (DMD) is one of the most common and severe. DMD affects one every 3,500 males born and is characterized by a progressive loss of muscular force, leading to wheelchair first and later complete paralysis and premature death. Currently many novel approaches such as exon-skipping, gene therapy and new drugs are in clinical experimentation, but it is highly unlikely that a single approach will be sufficient for all different types of mutations leading to DMD. The previous work of the investigators of the current protocol indicated that mesoangioblasts (MABS), a recently identified population of muscle progenitor cells, produce functional improvement upon intra-arterial injection in a mouse model of muscular dystrophy. Subsequently, transplantation of normal canine MABS gave promising results in the Golden Retriever dystrophic dog, the most reliable animal model that shows a form of dystrophy very similar to and even more severe than human Duchenne Muscular Dystrophy (DMD). Because of these results, and after careful studies of toxicology, biodistribution and validation of outcome measures, a pilot clinical trial will be conducted, based on intra-arterial transplantation of normal MABS from an HLA-matched sibling donor, under a regime of immune suppression. Cells will be expanded under clinical grade conditions and transplanted into the arterial circulation of pediatric dystrophic patients. Safety and efficacy in restoring at least in part muscle force will be the outcomes of this study that may represent a first step towards an efficacious therapy for muscular dystrophy.