ENZYME REPLACEMENT THERAPY FOR MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII LEADS TO IMPROVEMENTS IN BEHAVIOR AND AUDITORY FUNCTION

Mucopolysaccharidosis type VIP (MPS VII; Sly syndrome) is one of a gro up of lysosomal storage diseases that share many clinical features, in cluding mental retardation and hearing loss, Lysosomal storage in neur ons of the brain and the associated behavioral abnormalities character istic of a murine model of MPS VII have not been shown to be corrected by either bone marrow transplantation or gene therapy, However, intra venous injections of recombinant beta-glucuronidase initiated at birth reduce the pathological evidence of disease In MPS VII mice, In this study we present evidence that enzyme replacement initialed at birth i mproved the behavioral performance and reduced hearing loss in MPS VII mice, Enzyme-treated MPS VII mice performed similarly to normal mice and significantly better than mock-treated it?PS VII mice in every pha se of the Morris Water Maze test, In addition, the auditory function o f treated MPS VII mice was dramatically improved, and was Indistinguis hable from normal mice, These data indicate that some of the learning, memory, and hearing deficits can be prevented in MPS VII mice if enzy me replacement therapy is initiated early in life, These data also pro vide functional correlates to the biochemical and histopathological im provements observed after enzyme replacement therapy.