ENZYME REPLACEMENT THERAPY IN A FELINE MODEL OF MAROTEAUX-LAMY SYNDROME

We report studies that suggest enzyme replacement therapy will result in a significant reduction in disease progression and tissue pathology in patients with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). A feline model for MPS VI was used to evaluate tissue dis tribution and clinical efficacy of three forms of recombinant human N- acetylgalactosamine-4-sulfatase (rh4S, EC 3.1.6.1). Intravenously admi nistered rh4S was rapidly cleared from circulation. The majority of rh 4S was distributed to liver, but was also detected in most other tissu es. Tissue half-life was similar to 2-4 d. Three MPS VI cats given reg ular intravenous infusions of rh4S for up to 20 mo showed variable red uction of storage vacuoles in Kupffer cells and connective tissues, ho wever cartilage chondrocytes remained vacuolated. Vertebral bone miner al volume was improved in two MPS VI cats in which therapy was initiat ed before skeletal maturity, and increased bone volume appeared to cor relate with earlier age of onset of therapy. One cat showed greater mo bility in response to therapy.