A new global initiative launched today aims to close a critical gap in ALS/MND drug discovery - current cell models used for testing treatments do not currently reflect the diverse nature of the disease – that affects both researchers developing therapies and the people urgently waiting for them.
The ALS Therapy Development Institute (ALS TDI), LifeArc, and Axol Bioscience announced the launch of Patient induced pluripotent stem cell (iPSC)-based Research to Improve Sporadic ALS Modelling (PRISM), a collaborative effort to expand access to high-quality, patient-derived stem cell models that better reflect the biological complexity of amyotrophic lateral sclerosis (ALS).
ALS is a heterogeneous disease. While 10-15 % of cases are linked to inherited mutations, nearly 85 % are sporadic. Yet much of ALS drug discovery has relied on models representing a limited number of rare genetic subtypes. This mismatch has constrained target discovery, limited therapeutic testing across patient populations, and contributed to the high failure rate of clinical trials.
This unprecedented initiative will provide a reliable, high-quality, and accessible source of sporadic ALS/MND models for use in research. PRISM ALS aims to develop, evaluate, and make available a diverse panel of well-characterized, patient-derived induced pluripotent stem cell (iPSC) models that capture both genetic and sporadic forms of ALS.
For researchers and drug developers, those standardized, human-relevant models could allow them to better understand disease mechanisms, identify therapeutic targets, and evaluate treatments across distinct biological subtypes. For people living with ALS, it means therapies can be developed and tested in models that more closely mirror their own biology, increasing the likelihood that discoveries will translate into meaningful treatments.
The stem cells used in PRISM ALS are derived from samples contributed by people living with ALS through ALS TDI's ALS Research Collaborative (ARC) Study, the longest-running longitudinal patient study in ALS.
Over more than a decade, ALS TDI has built one of the most comprehensive collections of ALS-specific iPSCs available today. These cells come directly from people living with ALS, many of whom also contributed detailed clinical data, creating an unparalleled resource for understanding how the disease behaves and how it may respond to therapy.
This work is only possible because of the more than 1,800 people with ALS who have chosen to participate in the ARC Study and contribute samples and data to advance research.
We know that ending ALS will require delivering the right treatments to the right individuals. 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."
Dr. Fernando Vieira, CEO and Chief Scientific Officer, ALS TDI
By enabling standardized production at scale, the collaboration ensures quality, consistency, and reproducibility across laboratories. The goal is to accelerate progress across the ALS field by providing robust, human-relevant tools that better reflect the biological diversity and complexity of the disease.
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."
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."
By working together, the partners aim to ensure that these models become a widely accessible, high-quality resource for researchers in academia and industry who are committed to advancing ALS therapies.