A new global initiative aims to address long-standing limitations in amyotrophic lateral sclerosis (ALS) drug discovery by expanding access to patient-derived stem cell models designed to better reflect the biological diversity of the disease.

ALS Therapy Development Institute, LifeArc and Axol Bioscience have launched PRISM ALS, a collaboration focused on developing induced pluripotent stem cell (iPSC)-derived motor neuron models for use in research, therapeutic testing and clinical trial design.

The partners say the initiative is designed to address a key limitation in current ALS/MND drug discovery, where many preclinical models are based on rare genetic subtypes and do not fully capture sporadic disease, which accounts for the majority of cases.

By expanding access to well-characterised, patient-derived cell models, the consortium aims to improve how researchers study disease mechanisms, identify potential therapeutic targets and assess candidate treatments across different biological subgroups.

ALS is a highly heterogeneous neurodegenerative disease. Around 10–15% of cases are linked to inherited genetic mutations, while approximately 85% are sporadic, with no clear family history. Researchers say this variability has contributed to challenges in translating early-stage findings into successful late-stage clinical outcomes.

PRISM ALS will use samples collected through ALS Research Collaborative, a long-running patient study that has collected biological samples and clinical data from people living with ALS over more than a decade. More than 1,800 participants have contributed to the resource, which underpins the stem cell development programme.

The initiative will focus on generating standardised iPSC-derived cell models that can be distributed for use across academic and industry research settings, with the aim of improving reproducibility and enabling more consistent preclinical testing.

Dr Fernando Vieira, chief executive officer and chief scientific officer at ALS TDI, said: “By characterizing iPSC-derived motor neurons from sporadic ALS and making these cells broadly accessible, PRISM ALS will facilitate global drug discovery. This program is only possible thanks to the people living with ALS who contributed samples and data through the ARC Study.”

Sapna Vyas, head of scientific programs at Axol Bioscience, said: “We’re delighted to participate in this consortium to develop multiple iPSC-derived endpoint cell types from sporadic ALS iPSC lines that reflect real-world variability across age, sex and genotype.”

She added: “By leveraging scalable manufacturing infrastructure, we will facilitate access to standardized iPSC-derived cells that empower researchers to stratify patients, assess subgroup responses to therapies and reduce late-stage clinical trial failures.”

Paul Wright, head of MND at LifeArc, said: “Our hope is that the stem cell models we produce can support a new generation of treatments that slow disease progression and ultimately improve outcomes for people living with MND and ALS.”

Researchers involved in the initiative say that improving the biological relevance of preclinical models could help address one of the major challenges in the field: the high rate of failure in ALS clinical trials, where promising early signals often do not translate into efficacy in broader patient populations.

By standardising production and expanding access to diverse patient-derived models, PRISM ALS aims to support both target identification and more predictive testing of candidate therapies.

The partners say the long-term goal is to create a widely accessible resource for ALS research that better reflects disease variability and improves the likelihood that preclinical findings translate into meaningful clinical benefit.