Amelioration of clinical disease following bone marrow transplantation in fucosidase-deficient dogs.

Abstract

Canine fucosidosis was studied as an animal model for the treatment of neurovisceral lysosomal storage disease. Following successful bone marrow engraftment, dogs with fucosidosis had increased levels of alpha-L-fucosidase enzyme activity in leukocytes, plasma, and neural and visceral tissues. This widespread increase in enzyme activity was accompanied by a rapid improvement in the peripheral nerve and visceral lesions of fucosidosis and a more gradual improvement in the central nervous system pathology. Long-term engraftment from an early age reduced the severity and slowed the progression of clinical neurological disease. Transplantation after the onset of clinical signs was not effective. These findings suggest that the neurological damage caused by some inherited metabolic disorders, such as fucosidosis, may be preventable but emphasise the need for early diagnosis and treatment.