PRISM ALS Sets Out to Improve ALS/MND Drug Discovery
A new international collaboration is building more representative stem cell models of ALS, an effort that could improve drug discovery and reduce clinical trial failure rates.
A new global initiative is taking aim at a longstanding problem in ALS research: the models used to study the disease often fail to reflect the patients researchers are trying to help.
PRISM ALS, launched this week across Boston, London and Cambridge, brings together ALS Therapy Development Institute, LifeArc and Axol Bioscience. The goal is straightforward, but ambitious - to expand access to patient-derived stem cell models that better capture the biological complexity of amyotrophic lateral sclerosis (ALS), or motor neurone disease (MND).
The initiative, Patient induced pluripotent stem cell (iPSC)-based Research to Improve Sporadic ALS Modelling (PRISM), will focus on generating well-characterised iPSC-derived motor neuron models. Crucially, these are intended to represent not just rare genetic forms of ALS, but also the far more common sporadic cases.
The challenge in ALS drug discovery: models that don’t reflect sporadic disease
ALS has always been a difficult disease to study. Around 10–15% of cases are linked to inherited mutations, while roughly 85% are sporadic. Yet many of the models used in drug discovery are based on those rarer genetic subtypes.
That disconnect has had knock-on effects, limiting how well targets are validated, narrowing the scope of therapeutic testing, and, ultimately, contributing to the high attrition rate in clinical trials.
PRISM ALS is designed to address that gap by building a broader panel of models that better reflect real-world patient biology. For researchers, that should mean more relevant systems for studying disease mechanisms and testing therapies. For drug developers, it offers the possibility of identifying which approaches might work for which patient groups earlier in the pipeline.
Patient-derived iPSC models built on longitudinal ALS clinical data
The programme draws heavily on ALS TDI’s ALS Research Collaborative (ARC) Study, a longitudinal effort that has been running for over a decade. More than 1,800 people living with ALS have contributed samples and clinical data, creating a resource that links patient biology with disease progression.
That depth of data underpins what PRISM ALS is trying to achieve, which are models that are not only biologically, but also clinically, relevant.
“We know that ending ALS will require delivering the right treatments to the right individuals,”
Dr. Fernando Vieira, CEO and Chief Scientific Officer at ALS TDI.
“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.”
Scaling standardised iPSC stem cell models for ALS research and drug development
A key part of the collaboration is ensuring these models are not just developed, but actually usable at scale. Standardisation and reproducibility remain ongoing challenges in the field, particularly when working with complex human cell systems.
Axol Bioscience will play a central role here, providing the infrastructure to manufacture iPSC-derived cells in a consistent and scalable way.
Sapna Vyas, Head of Scientific Programs at Axol Bioscience, said:
“We’re delighted to participate in this consortium to develop multiple iPSC-derived end point cell types from sporadic ALS iPSC lines that reflect for the first time, real-world variability across age, sex, and genotype. By leveraging Axol’s 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.”
Improving ALS clinical trial success through more predictive disease models
Ultimately, the success of PRISM ALS will be measured by whether it improves translation, something the ALS field has struggled with for decades.
More representative models won’t solve every challenge, but they could make a meaningful difference. If therapies are tested in systems that better reflect patient diversity from the outset, there is at least a stronger chance that promising results will carry through into the clinic.
Paul Wright, Head of MND at LifeArc, added,
“Our hope is that the stem cell models we produce can unleash a new generation of treatments that could be effective against this disease by slowing its progression and, ultimately, curing it. We need to do more for people living with MND/ALS, and PRISM ALS brings together leading organizations to help make that happen.”
For now, PRISM ALS represents a coordinated attempt to fix a foundational issue in ALS research. If it delivers on that promise, it could quietly, but significantly, shift how the field approaches drug discovery.
Author
BioFocus Newsroom