iPSC-based Approaches to Amyotrophic Lateral Sclerosis: from Drug Screening to Regenerative Medicine in Early Clinical Translation.

Authors

Jessica Jianghan Lu, Martin Cheung

Published in

Stem cells (Dayton, Ohio). Nov 13, 2026. Epub Nov 13, 2026.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive loss of upper and lower motor neurons (MNs), with limited therapeutic options and modest benefit from currently approved drugs. Induced pluripotent stem cells (iPSCs) have emerged as a versatile platform for ALS research, enabling both regenerative medicine and phenotypic drug screening. iPSC-based transplantation strategies aim to replace lost cells or deliver neuroprotective support, while iPSC-derived MNs support drug discovery and repositioning. In the two decades since their discovery, iPSC technologies have progressed from concept to clinical translation, with both cell therapy products such as AstroRx and XS-228 entering trials and three screened drug candidates, Ropinirole, Bosutinib, and Ezogabine, advancing into clinical trials, underscoring their translational potential. In this review, we summarise iPSC-based approaches to ALS, focusing on cell therapies and drug discovery, highlight factors influencing transplantation success, and discuss ongoing clinical trials. We further discuss constraints that impede clinical trial progress, including limited understanding of ALS pathogenesis, absence of robust biomarkers to guide patient stratification and evaluate treatment response, and technical challenges related to the maturation of iPSC-derived neural cells. Finally, we advocate that advancing iPSC approaches requires both deeper understanding of ALS biology and technical innovation. Key priorities are refining iPSC differentiation protocols to improve neuronal maturity and implementing trial designs with adequate duration and rigorous patient stratification.

PMID:
43023417
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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