Long‐term beneficial effects of adrenal medullary autografts supported by nerve growth factor in Parkinson's disease

Abstract

Parkinson's disease has been the object of several therapeutic strategies based upon replacement of the degenerating dopaminergic neurons. Adrenal medullary transplants were tried initially, because of the biochemical relationship between chromaffin cells of the medulla and dopaminergic neurons of the substantia nigra. Compared to transplant of fetal neurons, autologous grafts of adrenal medullary tissue has the advantage of using a readily available source of tissue without the problems of immunosuppression. However, these cells have not proven to be as effective as fetal neurons, probably because they do not fully differentiate into neurons. In animal models, brief treatment with nerve growth factor can facilitate such differentiation. This study is a clinical evaluation of the efficacy of adrenal medullary cell transplantation, combined with nerve growth factor infusion. Two patients were selected who were moderately to severely affected (Hoehn-Yahr stage 2 in on-phase and stage 4 in off-phase). After adrenalectomy, small pieces of medulla were prepared and implanted stereotactically into the dorsal putamen on one side of the brain. A catheter filled with mouse beta-nerve growth factor (NGF) was placed close to the grafts. Infusion of NGF was continued for one month. Despite a progressively deteriorating course prior to surgery, both patients showed improvement on the rating scales postoperatively. There was also significant improvement in timed motor tests. Motor readiness evoked potentials showed increased voltage over the operated hemisphere. The study points to methods and feasibility of supplying nerve growth factor intraparenchymally to the human brain. Possible implications with respect to other growth factors, particularly Glial cell-line Derived Neurotrophic factor (GDNF) are discussed.