Cerebral transplantation for Parkinson's disease: current progress and future prospects.

Cerebral transplantation has received considerable attention from both the medical community and lay press as a potential treatment for Parkinson's disease. Animal models have demonstrated feasibility, although the experience in subhuman primates was very limited when the first human trials were initiated in the mid-1980s. The dramatic success reported for adrenal-to-brain transplantation in some initial trials could not be consistently replicated by other centers. Occasionally, however, patients benefited. Failure of the adrenal medullary graft to survive may have been a major factor in the poor outcomes. Recently, several US and European centers reported substantial clinical improvement after fetal dopaminergic mesencephalon was grafted into the striatum of patients with Parkinson's disease. Although many outcomes were impressive, in some cases the improvement was marginal; in no case was the condition completely reversed, and all but one patient still required levodopa therapy. Before this technique can be considered for routine use, further refinement is necessary, and many technical issues must be addressed. Certain animal studies have suggested that transplantation-related improvement may be derived from graft neurotrophic factors rather than from secretion of dopamine into the dopamine-depleted brain of patients with Parkinson's disease. Preliminary investigations in animals indicate that several other tissues, besides fetal mesencephalon, may also prove appropriate for grafting. Ultimately, advances in molecular biology may allow either transplantation of genetically engineered cells or direct modification of existing brain cells by transfection with viral vectors. The favorable preliminary experience with cerebral transplantation in patients with Parkinson's disease has resulted in the consideration of this strategy for other neurologic disorders.