Central Nervous System Grafting in the Treatment of Parkinsonism

Abstract

Central nervous System transplantation currently is being investigated in numerous Centers throughout the world. The concept of restoring lost neurological function by grafting neuronal or neuronal-like tissue into the CNS has the potential for revolutionizing the treatment of numerous neurological disorders. Parkinson''s disease is the subject of the majority of CNS transplantation studies although the first human studies were disappointing. However, further refinements of technique and patient selection, and animal research using a newly developed primate model of parkinsonism, led to promising results reported from several centers. Despite this, numerous fundamental issues have yet to be resolved: (1) age of patient? (2) degree of disability of patient? (3) use of fetal or adrenal tissue? (4) caudate or putamen placement? and (5) open or stereotactic surgery? This report reviews the clinically significant results of nonhuman primate research and clinical studies, and addresses these unresolved issues.

Preliminary Report on Adrenal-Brain Transplantation for Parkinsonism in Man

“…These cells may contribute to the behavioral improvement not so much through their production of dopamine, but through the stimula tion of a neurotrophic effect, as suggested by animal studies [3,8,9]. The necessity of an underlying substrate to produce sprouting in re sponse to a neurotrophic factor is suggested by the strong correlation with percent improvement and the number of surviving tyrosine hy droxylase positive boutons in the caudate.…”

“…They transplanted pieces of the entire adrenal medulla into a surgical bed prepared in the cau date, with a portion bathed by ventricular cerebrospinal fluid (CSF). After the report of success by the Mexican investigators, United States investigative teams [3] have begun to perform adrenal-caudate grafts in PD patients.…”

Neurosurgical Treatment of Movement Disorders: History and Update

“…77 Additional studies followed slowly, since the difficulties in obtaining and identifying the proper tissue, processing, and coordinating the implantation of fetal tissue were daunting. 85,86 Although survival of grafted cells and prolonged benefit have been shown, 87,88 unanticipated side effects and insurmountable organizational obstacles suggest that fetal transplantation will never be generally adopted.…”

Stereotactic Surgery –T he Past and the Future

“…They concluded that the results merit further clinical trials. Two years later, Madrazo et al [56] reported more favorable results [57], which provoked great interest, and many Gildenberg similar programs were begun [58][59][60]. Since results were sometimes found to be modest, the adrenal medulla is sometimes atrophic [62], and complications occurred due to the craniotomy when the tissue was placed by open surgery [63] (but very few using stereotactic techniques [64]), the procedure was essentially abandoned by 1991.…”

“…In 1989, 2 patients who received fetal cell transplantation for the treatment of Parkinson's disease were reported [65], and others followed soon after [60]. Although research in this area continues, this procedure is unlikely to become routine because of problems in obtaining fetal tissue at the proper age in the proper amounts, identification in the fetus of the proper tissue, processing of the tissue and coordination between obtaining the tissue and arranging for the implantation surgery [58,60,66].…”