Bone marrow transplantation does not ameliorate the neurologic symptoms inmice deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT)

The use of bone marrow transplantation (BMT) for the treatment of genetic d iseases with neurologic involvement has yielded mixed results. We have empl oyed a mouse model of Lesch-Nyhan disease (LND) to assess the efficacy of B MT in ameliorating the neurologic manifestations of the disease. Adult HPRT -deficient mice exhibit a measurable decrease in striatal dopamine levels a nd a hypersensitivity to amphetamine. Marrow-ablated adult HPRT-deficient m ice were transplanted with marrow from congenic HPRT-expressing mice. BMT a ltered neither the neurochemical nor the behavioral phenotypes in either HP RT-positive or HPRT-deficient mice. Barring any important species differenc es, these results suggest that BMT in its present form may not be an effect ive therapy for Lesch-Nyhan syndrome.