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Ropinirole Shows Promise in ALS Treatment by Extending Progression-Free Survival in Phase 1/2a Trial

• A Phase 1/2a trial of ropinirole in sporadic ALS patients demonstrated acceptable safety and tolerability over 24 weeks. • While the ALSFRS-R decline was not significantly different during the double-blind phase, muscle strength and daily activity were maintained. • The open-label extension showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival in the ropinirole group. • The study suggests a potential therapeutic effect of ropinirole in ALS, possibly involving the SREBP2-cholesterol pathway, warranting further investigation.

An experimental treatment for amyotrophic lateral sclerosis (ALS), ropinirole, has shown promising results in a Phase 1/2a clinical trial. The study, which utilized iPSC-based drug discovery, evaluated the safety, tolerability, and therapeutic effects of ropinirole in 20 participants with sporadic ALS. The findings suggest that ropinirole may extend disease-progression-free survival, offering a potential new avenue for ALS treatment.

Initial Safety and Tolerability

During the 24-week double-blind period, participants received either ropinirole or a placebo. The adverse event profiles were similar between the two groups, indicating that ropinirole was generally safe and well-tolerated. While there was no statistically significant difference in the decline of ALSFRS-R scores (a measure of functional status in ALS patients) compared to the placebo group during this phase, muscle strength and daily activity levels were maintained in the ropinirole group.

Extended Progression-Free Survival

The open-label extension period revealed a more compelling outcome. Patients treated with ropinirole demonstrated a significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival compared to the placebo group. This suggests a potential long-term benefit of ropinirole in slowing the progression of ALS.

Mechanistic Insights

Further investigation into the mechanisms of action revealed that iPSC-derived motor neurons from participants expressed dopamine D2 receptors. This finding, coupled with the observed therapeutic effects, points to a potential involvement of the SREBP2-cholesterol pathway in mediating the benefits of ropinirole. Lipid peroxide was identified as a potential clinical surrogate marker for assessing disease progression and drug efficacy.

Limitations and Future Directions

The study acknowledges limitations, including the small sample size and high attrition rates during the open-label extension period. These factors necessitate further validation in larger, more comprehensive clinical trials. Despite these limitations, the results offer a signal of potential efficacy and warrant continued exploration of ropinirole as a treatment for ALS.
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Reference News

[1]
Phase 1/2a clinical trial in ALS with ropinirole, a drug ...
sciencedirect.com · Jun 1, 2023

A phase 1/2a trial tested ropinirole in 20 ALS patients, showing similar adverse events in ropinirole and placebo groups...

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