Novel human trial finds A-dopamine continuous intracerebroventricular administration safe for Parkinson’s disease

PHILADEPHIA, USA —Continuous intracerebroventricular (i.c.v.) infusion of anaerobic dopamine (A-dopamine) has been demonstrated as feasible and safe for patients experiencing complications from traditional dopamine medications, according to a study released today at the International Congress of Parkinson’s Disease and Movement Disorders^® in Philadelphia.

Continuous administration of levodopa, a common dopaminergic therapy for patients with Parkinson’s’ disease, has presented challenges such as short half-life, excess peripheral distribution, and restricted absorption.¹ Continuous i.c.v. administration of A-dopamine prevents dopamine oxidation and has been shown to be safe and effective in rodent and non-human primate models of Parkinson’s disease (PD).

The study by Moreau et al. included two phase components. Phase 1 concluded safety of the approach. Phase 2 compared one month of A-dopamine administration to one month of standard oral dopaminergic medication. All phase 2 participants showed a significant reduction in medication side effects (off-time and dyskinesias) and did not experience induced dyskinesia or adverse effects.

“These findings provide compelling evidence that continuous dopaminergic stimulation via i.c.v. A-dopamine can offer substantial clinical improvements in motor disability, likely due to the reduction in motor complications typically associated with oral therapies,” said Andrew Evans, neurologist at the Royal Melbourne Hospital, “Remarkably, the absence of dyskinesia with continuous A-dopamine infusion suggests that this approach may have the potential to reverse the aberrant plasticity in the corticobasal ganglia system — a key factor in the pathophysiology of L-dopa-induced dyskinesia and its associated neurobehavioral issues.

“While this study is small and the long-term risks of continuous i.c.v. A-dopamine administration remain unknown, the promising results warrant further investigation. This novel approach could ultimately offer superior outcomes compared to existing therapies, such as the direct delivery of continuous gel L-dopa to the duodenum or subcutaneous apomorphine infusions.”

Full text of this abstract will be available at mdsabstracts.org (Reference #675) after the embargo lifts September 27, 2024, 08:00 ET. 
 

References

1. Demailly A, Moreau C, Devos D. Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics. J Parkinsons Dis. 2024;14(5):925-939. doi: 10.3233/JPD-230372. PMID: 38848195; PMCID: PMC11307025.

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About the 2024 MDS International Congress of Parkinson’s Disease and Movement Disorders^®:  
The MDS International Congress is the premier annual event to advance the clinical and scientific discipline of Movement Disorders, including Parkinson’s disease. Convening thousands of leading clinicians, scientists and other health professionals from around the globe, the International Congress will introduce more than 1,800 scientific abstracts and provide a forum for education and collaboration on latest research findings and state-of-the-art treatment options. Learn more at www.mdscongress.org. 

About the International Parkinson and Movement Disorder Society: 
The International Parkinson and Movement Disorder Society^® (MDS), an international society of more than 11,000 clinicians, scientists, and other healthcare professionals, is dedicated to improving patient care through education and research. For more information about MDS, visit www.movementdisorders.org.