External and implanted pumps for apomorphine infusion in parkinsonism

Area of Science:

• Neuroscience
• Pharmacology
• Neurology

Background:

• Continuous dopaminergic agent delivery to the striatum is crucial for Parkinson's disease (PD) treatment.
• Apomorphine, a D1 and D2 receptor agonist with good solubility, is a promising candidate for PD therapy.
• Managing severe L-dopa-induced motor fluctuations remains a significant clinical challenge.

Purpose of the Study:

• To evaluate the efficacy and tolerability of continuous subcutaneous (SC) apomorphine infusion in Parkinsonian patients.
• To assess the feasibility and effects of intracerebroventricular (ICV) apomorphine administration in MPTP-treated monkeys.

Main Methods:

• Seventeen Parkinsonian patients with severe L-dopa-induced on-off effects received continuous SC apomorphine via minipumps.
• Seven macaca fascicularis monkeys received ICV apomorphine using implanted programmable pumps; four were induced with MPTP.
• Motor function and side effects were monitored in both patient and animal models.

Main Results:

• SC apomorphine reduced daily 'off' periods in patients by 61%.
• SC nodules were observed in all patients, limiting external infusion feasibility.
• ICV apomorphine in monkeys increased cerebrospinal fluid (CSF) concentrations and improved motor function in MPTP models.
• Long-term ICV administration was limited by catheter issues and potential apomorphine toxicity.

Conclusions:

• Continuous SC and ICV apomorphine infusions demonstrate efficacy in controlling Parkinsonian motor activity.
• While effective, SC infusion presents tolerability challenges (nodules), and ICV administration faces long-term toxicity and technical hurdles.
• Further research is needed to address long-term toxicity and optimize delivery methods for Parkinson's disease management.