NEURAL TRANSPLANTATION FOR HUNTINGTONS-DISEASE - EXPERIMENTAL RATIONALE AND RECOMMENDATIONS FOR CLINICAL-TRIALS

Huntington's disease (HD) is a neurodegenerative disorder affecting mo tor function, personality, and cognition, This paper reviews the exper imental data that demonstrate the potential for transplantation of fet al striatum and trophic factor secreting cells to serve as innovative treatment strategies for HD. Transplantation strategies have been effe ctive in replacing lost neurons or preventing the degeneration of neur ons destined to die in both rodent and nonhuman primate models of HD, In this regard, a Logical series of investigations has proven that gra fts of fetal striatum survive, reinnervate the host, and restore funct ion impaired following excitotoxic lesions of the striatum, Furthermor e, transplants of cells genetically modified to secrete trophic factor s such as nerve growth factor protect striatal neurons from degenerati on due to excitotoxicity or mitochondrial dysfunction, Given the disab ling and progressive nature of HD, coupled with the absence of any mea ningful medical therapy, it is reasonable to consider clinical trials of neural transplantation for this disease, Fetal striatal implants wi ll most likely be the first transplant strategy attempted for HD, This paper describes the variable parameters we believe to be critical for consideration for the design of clinical trials using fetal striatal implants for the treatment of HD.