Preliminary Report on Adrenal-Brain Transplantation for Parkinsonism in Man

Abstract

The attempt to restore lost neurological function through grafting of cate-cholaminergic tissue into the striatum is a dramatic new experimental treatment approach for parkinsonism. We have grafted autologous adrenal medullary tissue into the right caudate nucleus in 12 patients with advanced Parkinson''s disease (10 males, 2 females, mean age 53 years, mean Hoehn and Yahr stage ‘off’ medications 4.2) applying a transcortical technique similar to that of Madrazo as modified by Allen using right adrenalectomy performed via a flank approach. There have been no deaths, surgical complications, or serious postoperative morbidity. Modified Columbia Parkinson''s disease ratings of patients of all dopaminergic agents for 72 h revealed 22% improvement (p < 0.01) 3–6 months postoperatively (n = 10) and 22% improvement (p < 0.01) 7–12 months later (n = 9). Postoperative dyskinesias necessitated reduction of L-dopa by 11% and of carbidopa by 29%. Analysis of lumbar cerebrospinal fluid biogenic amine metabolites following a 4-day ''drug holiday'' revealed that homovanillic acid increased to 159% of preoperative levels (p < 0.01) 3–6 months (n = 9) and to 197% of preoperative levels (p < 0.02) 7–12 months postoperatively (n = 5). We have observed a mild to moderate improvement persisting up to 1 year with this therapeutic approach, but further study is needed.

Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease

“…In the second experiment, which was conducted to investigate whether or not functional improvement resulted from cholinergic neuron reinnervation by the graft; similar recovery was observed in rats with noncholinergic neuron implantation as well as rats with cholinergic neuron The first mechanism is that graft tissue survives, and functions as a store releasing deficient neurotransmitters. Partial recovery observed in sensorimotor and behavioral disorders after adrenal medulla grafts in Parkinson disease (PD) model, and peripheral cholinergic ganglion grafts in AD model reinforces these mechanisms (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54).…”

“…In the study performed with hemiparkinsonism model in monkeys, Bankiewicz et al (23) reported that locomotor activity was recovered by both cavitations opened in caudate nucleus and dopaminergic and nondopaminergic tissue transplantations. In the study, dopaminergic axons extending from recipient neural tissue to the graft and cavity were detected (46,51,80). These findings indicated that functional recovery was obtained as the result of recipient neural tissue, itself, started to build up the damaged connections by using trophic mechanisms stimulated by cavitation and implantation.…”