Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery

GPCR（IDP）の一種であるdopamine D2 receptorに対するagonist（ropinirole hydrochloride）が、筋萎縮性側索硬化症（ALS）へ与える影響について、基礎-臨床一体型の研究により明らかにしました。

Abstract: iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

Author: Morimoto S, Takahashi S, Ito D, Daté Y, Okada K, Kato C, Nakamura S, Ozawa F, Chyi CM, Nishiyama A, Suzuki N, Fujimori K, Kondo T, Takao M, Hirai M, Kabe Y, Suematsu M, Jinzaki M, Aoki M, Fujiki Y, Sato Y, Suzuki N, Nakahara J; Pooled Resource Open-Access ALS Clinical Trials Consortium; Okano H.

Journal: Cell Stem Cell 2023;30(6):766-780.