Skeletal disease is prevalent in most mucopolysaccharidosis (MPS) subtypes, particularly in the spine, where vertebral dysplasia leads to progressive  def01mity  and spinal cord compression. Resulting pain and paralysis significantly diminish patient quality of life and   increase m01iality. MPS VII patients exhibit severe spine disease for which there are currently no effective treatments. Previously, using the natural-occurring canine model of MPS VII, we established that vertebral bone formation is delayed, non-uniform and incomplete during postnatal growth. Wnt/B-catenin signaling is a crucial positive regulator of bone formation and our preliminary data suggests impaired activation of this pathway coincident with the earliest manifestations of bone disease in MPS VII dogs. Our overall objective in this proposal is to investigate the role of Wnt/B-catenin signaling dysregulation in the etiology of failed vertebral bone formation in MPS VII and establish this pathway as a viable therapeutic target.

–  Dr. Lachlan J. Smith

University of Pennsylvania Philadelphia, PA