Long-term neurological effects of bone marrow transplantation in a canine lysosomal storage disease

Abstract

A naturally occurring disease in Plott hound dogs, caused by deficiency of the lysosomal enzyme α-L-iduronidase, was used to study the feasibility of bone marrow transplantation therapy in a neurodegenerative storage disease. Three long-term survivors of transplantation with littermate marrow at 5 months of age (before clinical signs) had CNS enzyme activity, glycosaminogly-can storage, and light microscopic and ultrastructural changes evaluated 594, 628, and 740 days after treatment. Iduronidase activity in small amounts (1-3% of donor values) was detectable in brain tissue. Cerebrospinal fluid had higher iduronidase activity after transplantation (715% of donor values). Enzyme activity within the CNS resulted in significant reductions in stored glycosaminogly-cans and resolution, to a large extent, of light microscopic and ultrastructural lesions observed in affected, untreated littermate control dogs. © 1988 International Pediatric Research Foundation, Inc.