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

A naturally occurring disease in Plott hound dogs, caused by deficiency of the lysosomal enzyme alpha-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, glycosaminoglycan 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 (7-15% of donor values). Enzyme activity within the CNS resulted in significant reductions in stored glycosaminoglycans and resolution, to a large extent, of light microscopic and ultrastructural lesions observed in affected, untreated littermate control dogs.