Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology

Neural and stem cell transplantation is emerging as a potential treatment f or neurodegenerative diseases. Transplantation of specific committed neurob lasts (fetal neurons) to the adult brain provides such scientific explorati on of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) n eurodegenerative disorder with primary neuronal pathology within the caudat e-putamen (striatum). In a clinical trial of human fetal striatal tissue tr ansplantation, one patient died 18 months after transplantation from cardio vascular disease, and postmortem histological analysis demonstrated survivi ng transplanted cells with typical morphology of the developing striatum. S elective markers of both striatal projection and interneurons such as dopam ine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, cho line acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and su bstance P showed positive transplant regions clearly innervated by host tyr osine hydroxylase fibers. There was no histological evidence of immune reje ction including microglia and macrophages. Notably, neuronal protein aggreg ates of mutated huntingtin, which is typical HD neuropathology, were not fo und within the transplanted fetal tissue. Thus, although there is a genetic ally predetermined process causing neuronal death within the HD striatum, i mplanted fetal neural cells lacking the mutant HD gene may be able to repla ce damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue ca n survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD.