Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron (MN) degeneration. Ropinirole hydrochloride (ROPI), a dopamine receptor D2 (DRD2) agonist, was identified through phenotypic screening of MNs derived from patient-derived induced pluripotent stem cells (iPSCs) as a disease model and has emerged as a promising candidate drug for ALS treatment. The ROPALS trial, a phase I/IIa trial in patients with ALS, suggested the safety and efficacy of ROPI, albeit in a small sample size. Interestingly, a DRD2 antagonist and modulator only partially mitigated the suppressive effect of ROPI on the ALS phenotype, and the detailed mechanism of ROPI activity remains unclear. Therefore, in this study, we investigated whether the therapeutic effects of

SUBMITTER: Asano H 

PROVIDER: S-EPMC12361731 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature