Pharmacological neuromodulation by intracerebroventricular administration of anaerobic dopamine in the treatment of advanced Parkinson's disease

Abstract

Continuous compensation of cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. However, dopamine does not cross the digestive and blood-brain barriers, and is rapidly oxidised. The new concept is continuous intra-cerebroventricular administration of anaerobic dopamine (A-dopamine) using a telemetry-controlled subcutaneous abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum. A phase I study was conducted showing no serious A-dopamine-induced adverse events in 12 patients, followed by a randomised, controlled, open-label, cross-over, phase II study of 1 month of A-dopamine vs. 1 month of optimised oral antiparkinsonian therapy. The primary endpoint, a blinded assessment of the percentage over the total target (i.e. time with dyskinesia or bradykinesia), recorded by actimetry at home using a wristwatch, was significantly reduced. All expected secondary clinical outcomes were significantly improved, providing the first promising data on the feasibility, safety and efficacy of this new device aided therapy for advanced stage patients. ClinicalTrials.gov identifier:NCT04332276