This application is for support to conduct a controlled clinical trial to evaluate the safety and efficacy of methionine in the treatment of AIDS myelopathy and dementia. The hypothesis is that abnormal metabolism of methionine may play an important role in the pathogenesis of vacuolar myelopathy. Methionine is a direct precursor of S-adenosyl methionine (SAM), the major methyl group donor in the nervous system. Vacuolar myelopathy is similar to the myelopathy of vitamin B12 deficiency, and can be induced by blocking methionine-synthetase and decreasing production of methionine. The result is decreased production of cystathionine and glutathione, rendering the CNS more vulnerable to oxidative stress. In experimental models, myelopathy caused by methionine synthase block can be abrogated by treatment with methionine. Finally, in AIDS, methionine levels in plasma and CSF are low. In the pilot studies, the Principal Investigator demonstrated clear clinical improvement of AIDS patients following treatment with oral methionine, thereby justifying a more extensive and double-blinded trial. The primary specific aim is to assess the efficacy of methionine in improving the clinical manifestations of AIDS-associated vacuolar myelopathy, and the safety and tolerability of oral methionine in the treatment of AIDS myelopathy. The secondary specific aim is to assess the efficacy of methionine in improving central conduction time of somatosensory evoked potentials and cognitive functions, and to evaluate serum levels of methionine, SAM, cystein homocysteine and glutathione in relation to severity of myelopathy in patients with AIDS vacuolar myelopathy, before and after treatment with methionine.
