Largest ALS patient-based iPSC repository opens new frontiers in research

In a landmark continuing collaboration, Answer ALS and Cedars-Sinai have announced the completed availability of the largest amyotrophic lateral sclerosis (ALS) patient-based induced pluripotent stem cell (iPSC) and bio data repository. The repository encompasses biological and clinical data from nearly 1,000 ALS patients, offering an unprecedented resource for global researchers studying ALS, commonly known as Lou Gehrig's disease.

Led by Dhruv Sareen, Ph.D., Executive Director of the Cedars-Sinai Biomanufacturing Center, the team, which includes Biomanufacturing Center Manager Loren Ornelas and Associate Biomedical Scientist Aaron Frank, has achieved a milestone in ALS research.

We reprogrammed blood cells into iPSCs and differentiated them into motor neurons, which die in ALS patients at an unprecedented scale. This has established the world's largest bank of specialized neurons for ALS research to date and offers a comprehensive and advanced model for disease research and drug discovery."

 Dhruv Sareen, Ph.D., Executive Director of the Cedars-Sinai Biomanufacturing Center

This approach enables investigators across academia and industry to access a vast array of patient-specific iPSCs and differentiated motor neurons. They can then analyze ALS disease progression in lab-created cells and correlate these observations with the detailed clinical, genetic, and protein profiles unique to each ALS patient.

The availability of an ALS patient's "avatar-in-a-dish" with an extensive selection of multi-omics data is critical for understanding the unique characteristics of ALS in individuals, paving the way for tailored therapeutic strategies. Unlike mouse models, patient-specific iPSCs embody the full complexity of human biology-;including genetic, epigenetic, transcriptomic, and proteomic profiles-;offering a more comprehensive and precise means to study disease mechanisms and evaluate potential treatments. This represents a pivotal advancement in ALS research, significantly enhancing our ability to address this challenging and devastating disease. 

These data and links to the associated bio-resources (tools, patient-derived biofluids, iPSC lines) are made available to the global research community through the Answer ALS Neuromine Data Portal, and Cedars-Sinai Biomanufacturing Center, which serves as a crucial tool for researchers, offering access to a wide array of patient-specific iPSCs and the data inherent in these cells. The availability of detailed genomic data is imperative for understanding the unique characteristics of the disease in individuals, paving the way for tailored therapeutic strategies.

"ALS remains one of the most challenging neurological diseases, with no cure and limited treatment options. Creating high-quality ALS iPSC lines and generating neurons from them at this scale is unprecedented," said Clive Svendsen, Director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai. "We believe this comprehensive platform will serve as a critical resource for the scientific community, propelling research into ALS pathogenesis, therapeutic development, and precision medicine approaches. The availability of this biorepository and the integration of a rich multi-omics dataset allows investigation of complex biological networks that drive ALS. We are offering these essential patient cells to the entire research community via the Cedars-Sinai Biomanufacturing Center biorepository as part of the Neuromine data portal resources."

The repository has already distributed over 1,800 cell lines to over 130 entities, including universities and pharmaceutical companies both domestically and internationally. By making the Answer ALS data continuously available through an online, open-source portal, the repository ensures that the data from every sample is accessible to scientists worldwide, enhancing the collective effort to decipher ALS pathology and develop targeted therapies.

"This model has never existed before at this scale; it surpasses traditional methods and has the potential to dramatically accelerate the pace of ALS research," said Clare Durrett, Managing Director of Answer ALS. "By making these high-quality, patient-specific iPSCs available to the scientific community, we are directly supporting the urgent efforts to develop effective treatments for individuals and families affected by ALS, where every second counts in the fight against this disease."

The repository represents a quantum leap over existing models, also providing ready-to-investigate motor neurons in just 7-10 days-;compared to the approximately 45 days typically required to generate motor neurons from iPSCs-;and offering efficiency that is crucial for fast-tracking the development of effective ALS treatments. With this largest-ever repository of patient-derived iPSCs and motor neurons for ALS research, complemented by a rich multi-omics dataset, the transformative potential of this platform will empower expanded collaborations with international research and biotech communities.