Intraputaminal Infusion of Nerve Growth Factor to Support Adrenal Medullary Autografts in Parkinson's Disease

Abstract

Experimental studies in rodents show that beta-nerve growth factor can increase the survival, neurite outgrowth, and functional effect of grafts of adrenal chromaffin cells to the basal ganglia. We, therefore, have begun to investigate whether treatment with nerve growth factor might also increase the functional effect of autografts of adrenal medullary tissue in patients with Parkinson's disease. Previous studies have shown that stereotactic implantation of adrenal tissue pieces produces a transient functional improvement that lasts for a few months. This report describes a trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor. The patient is a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia, despite optimized medical management. The left adrenal gland was removed, and the medulla was dissected into 1- to 2-mm3 pieces in a solution containing nerve growth factor purified from mouse submandibular gland. Pieces were implanted in six tracts 3 to 4 mm from a previously placed cannula in the left putamen. Through the cannula, nerve growth factor was infused for 23 days for a total dose of 3.3 mg. Clinical assessment consisted of global ratings for rigidity and/or hypokinesia and for drug-induced hyperkinesia. Measures of gait and fine-motor control were also made. The motor readiness potential and auditory evoked potentials were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)