Huntington's disease (HD) is a dominantly inherited condition, resulting from excessive repetition of the codon CAG within the IT 15 gene on the short arm of chromosome 4. Animal studies have demonstrated that glutamatergic NMDA receptor mediated neurotransmission increases the demand for energy metabolism and creates brain lesions that mimic the pathology of HD. The systemic or intraparenchymal administration of agents that impair energy metabolism also produce HD-like lesions which can be attenuated by blockers of NMDA subtypes of glutamate receptors and by free radical scavengers. Both glutamate mediated and bioenergetic insults cause free-radical production and elevations of lactate in brain. Lactate accumulation has been observed in the brains of patients with HD and can be reduced by treatment with electron transport enhancer and free radical scavenger Coenzyme Q10 (CoQ). Both Co Q, an over-the-counter nutritional supplement, and remacemide hydrochloride, a blocker of NMDA receptor mediated ion channels have been found to be well tolerated in HD patients. The primary hypothesis of this study is that chronic treatment of HD patients with CoQ and remacemide, alone or in combination, will slow the progression of the clinical features of HD and will be well tolerated.
The specific aim of the study is to investigate this hypothesis in a double-blind, placebo- controlled, randomized, parallel group, multi-center study of Co Q and remacemide in a 2 X 2 factorial design in 340 ambulatory HD patients for 31 months. 16 patients will be enrolled at the Columbia site. The primary outcome measure will be the change in clinical features of HD as indicated by subjects' functional capacity at baseline and 30 months.
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