FUNCTIONAL-INTEGRATION OF STRIATAL ALLOGRAFTS IN A PRIMATE MODEL OF HUNTINGTONS-DISEASE

Huntington's disease is an autosomal dominant, inherited disorder that results in progressive degeneration of the basal ganglia (especially the neostriatal caudate nucleus and putamen) and other forebrain struc tures and is associated with a clinical profile of movement, cognitive and psychiatric impairments for which there is at present no effectiv e therapy(1). Neuropathological, neurochemical and behavioral features of the disease can all be reproduced in experimental animals by local injection of excitotoxic(2,3) or metabolic(4,5) toxins into the neost riatum. All these features of the disease can be alleviated, at least in rats, by transplantation of embryonic striatal tissue into the dege nerated striatum(6-8), which was the basis for commencing the first cl inical trials of striatal transplantation in Huntington's patients(9,1 0). However, although rat striatal xenografts may temporarily reduce a pomorphine-induced dyskinesias in monkeys(11), there has been no demon stration that allograft techniques that work well in rats translate ef fectively to the much larger differentiated striatum of primates(12). Here we demonstrate good survival, differentiation and integration of striatal allografts in the primate neostriatum, and recovery in a test of skilled motor performance. Long-term graft survival in primates in dicates probable success for clinical transplants in Huntington's dise ase; in addition, our data suggest that graft placement has a direct i nfluence on the pattern and extent of functional recovery.