Objective: We aim to demonstrate the safety and efficacy of continuous circadian intracerebroventricular (i.c.v.) administration of anaerobic-dopamine (A-dopamine) to reduce the L-dopa-related complications (LDRC) in PD patients.

Background: Continuous compensation of dopamine represents an ideal symptomatic treatment for Parkinson’s disease (PD). The feasibility in administration (i.c.v.) of dopamine previously failed because of unresolved dopamine oxidation. We have circumvented this obstacle by preparing and preserving the dopamine in anaerobic without preservatives.

Method: A phase I safety study with titration until satisfactory control of LDRC followed by a phase IIb efficacy study with a crossing over design of two 1-month periods (open-label with randomization): i.c.v. A-dopamine versus optimized oral medical treatment at the stage of severe LDRC. A-dopamine (50 mg/ml or 100 mg/ml concentration) is contained in a pump implanted in the abdominal region and connected by a subcutaneous catheter to the frontal horn of the right ventricle, at the entrance of the 3rd ventricle (adjacent to the striatum). The telemetry adjustment ensures continuous and personalized delivery with transcutaneous refill every 7 to 21 days. Patients were regularly assessed by diaries and actimetry at home.

Results: Four patients have been included and 8 additional patients are planned from April to December 2022. No serious adverse events were observed in relation to treatment. The main adverse events were nausea and drowsiness when titrated too quickly. No recurrence of addictive behavior or hallucinations was observed. The dose of approximately 100 mg/24h allowed a reduction of the oral treatment by 40%, with a reduction of dyskinesias by 80% and of severe “off” periods by 75% compared to the oral treatment. The dose of about 200 mg/24h allowed a reduction of the oral treatment by 70% with a quasi-disappearance of dyskinesias and severe “off” periods with persistence of short “off” periods. All patients requested long-term continuation of the treatment in compassionate use with transcutaneous home refill (18 months for patient 1 in March 2022).

Conclusion: Continuous circadian i.c.v. of A-dopamine appears to be very safe and highly efficient to reduce LDRC and notably dyskinesia with a large therapeutic index.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/continuous-circadian-intracerebroventricular-administration-of-anaerobically-preserved-dopamine-greatly-reduces-severe-l-dopa-related-complications-in-parkinsons-disease/