Mucopolysaccharidosis IVA (MPS IVA: Morquio A syndrome) is caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme progressively causes accumulation of the glycosaminoglycans keratan sulfate and chondroitine-6-sulfate in multiple tissues (especially bone, cartilage, heart valves, and cornea), and leads to a unique form of skeletal dysplasia. Enzyme replacement therapy (ERT) for MPS IVA has been recently approved by the FDA. However, weekly ERT has a limited impact on bone abnormalities, and current therapies do not relieve skeletal symptoms in MPS IVA. Therefore, a novel therapy for MPS IVA is required to prevent or rescue the skeletal abnormalities. Gene therapy is a regenerative medicine that is expected to provide a one-time permanent treatment since the active enzyme is secreted continuously by transduced cells into the circulation. As yet, there are no in vivo reports on MPSIVA gene therapy. To assess the effect of gene therapy on skeletal disorders of MPS IVA, we will evaluate the effect of two gene vectors to replace the deficient enzyme in a MPS IVA mouse model. We hypothesize that the proposed gene vectors will have a significant impact on bone and cartilage lesions in MPS IVA.
– Dr. Kazuki Sawamoto, Dr. Shunji Tomatsu
Nemours/Alfred I. duPont Hospital for Children Wilmington, DE