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.

基于 iPSC 的药物发现促成了罗匹尼罗在 ALS 中的 1/2a 期试验。20 名散发性 ALS 参与者在双盲期接受罗匹尼罗或安慰剂治疗 24 周，以评估安全性、耐受性和治疗效果。两组的不良事件相似。在双盲期间，肌肉力量和日常活动得以维持，但评估 ALS 患者功能状态的 ALSFRS-R 的下降与安慰剂组没有差异。然而，在开放标签延长期内，罗匹尼罗组显示出对 ALSFRS-R 下降的显着抑制和额外的 27.9 周无疾病进展生存期。来自参与者的 iPSC 衍生的运动神经元表现出多巴胺 D2 受体表达和 SREBP2-胆固醇通路在治疗效果中的潜在参与。过氧化脂质是评估疾病进展和药物疗效的临床替代标志物。局限性包括样本量小和开放标签延长期内的高损耗率，需要进一步验证。