ロピニロール塩酸塩—iPS細胞創薬

Ropinirole Hydrochloride for ALS

2018年12月より，筋萎縮性側索硬化症（ALS）患者に対するロピニロール塩酸塩の安全性・忍容性および有効性を探索するプラセボ対照，二重盲検期および非盲検継続投与期から成る第Ⅰ/Ⅱa相試験を開始した。ロピニロール塩酸塩は，家族性および孤発性ALS患者の疾患特異的iPS細胞（iPSC）を用いて作成された脊髄運動ニューロンのin vitro疾患表現型を抑制し得る薬剤として，1,232種類の既存薬ライブラリーからスクリーニングされた薬剤であり，本試験の成否は今後のiPSC創薬研究の試金石となる。

Abstract

Our laboratory previously established spinal motor neurons (MN) from induced-pluripotent stem cells (iPSCs) prepared from both sporadic and familial ALS patients, and successfully recapitulated disease-specific pathophysiological processes. We next searched for effective drugs capable of slowing the progression of ALS using a drug library of 1232 existing compounds and discovered that ropinirole hydrochloride prevented MN death. In December 2018, we started an investigator-initiated clinical trial testing ropinirole hydrochloride extended-release tablets in ALS patients. This is an on-going phase I/IIa randomized, double-blind, placebo-controlled, single-center, open-label continuation clinical trial (UMIN000034954). The primary aim is to assess the safety and tolerability of ropinirole hydrochloride in patients with ALS. We will also perform an efficacy evaluation using patient-derived iPSCs/MN. Major inclusion criteria were as follows: 1) ‘clinically possible and laboratory-supported ALS’, ‘clinically probable ALS’ or ‘clinically definite ALS’, according to the criteria for the diagnosis of ALS (El Escorial revised) and within 60 months after disease onset; 2) change in ALSFRS-R score of -2 to -5 points during the 12-week run-in period. Finally, 15 patients will be assigned to the active drug and 5 patients to the placebo. Our trial will be a touchstone trial for iPSC-based drug development strategies.