Long-term effects of bone marrow transplantation in dogs with mucopolysaccharidosis I.

The therapeutic effects of allogeneic bone marrow transplantation (BMT) in a canine model of mucopolysaccharidosis I (MPS I) were investigated. Long-term post-BMT pathologic and biochemical studies were performed on three groups of dogs: 1) MPS I-affected dogs that did not receive BMT, 2) MPS I-affected dogs that received total body irradiation followed by an allogeneic BMT, and 3) normal, unaffected dogs that served as BMT donors. All dogs were necropsied at approximately 20 months after BMT. The severity of MPS I-related lesions in the dogs receiving BMT was greatly diminished. These dogs had only slight cardiac valvular thickening, no meningeal thickening, no renal tubular epithelial vacuolation, decreased neuronal vacuolation, decreased corneal stromal vacuolation, and greatly diminished arterial medial thickening. The severity and incidence of degenerative arthropathy also were decreased in BMT dogs, however, vertebral lesions were similar to nontransplanted, affected dogs. Chondrocytes of both MPS I-BMT and MPS I-no BMT groups had similar marked cytoplasmic vacuolation, except for MPS I-BMT chondrocytes near the articular surface, which had more normal morphology. Ultrastructurally, the liver and kidney tissue in BMT recipients had no appreciable lysosomal accumulation of GAGs. These morphologic findings were supported by near normal levels and electrophoretic patterns of glycosaminoglycans (GAG) in most tissues of BMT recipient dogs. This study demonstrates that BMT is capable of substantially diminishing the severity of MPS I-related lesions in this canine model.