At Target ALS, our mission is to break down barriers to ALS research to find effective treatments. Our Research Cores provide essential tools to academic and industry scientists worldwide who are conducting critical work to understand ALS biology better and develop biomarkers and therapeutics. One key tool for researchers studying neurodegenerative diseases like ALS is a suite of induced pluripotent stem cells (iPSCs) generated from donated tissue from individuals living with ALS. iPSCs are made from skin or blood cells and maintain the genetic information of the individual donor. During ALS research, iPSCs can be turned into disease-relevant cell types, like motor neurons or nervous system immune cells called microglia and astrocytes. Researchers can use these cells to study which biological factors contribute to disease and they can test candidate drugs on these cells to help predict whether the treatment would be beneficial in people living with ALS. Historically, scientists have not had access to human stem cells and therefore used animal models and other cell-based models that are biologically quite different from humans and can lead to misleading data and lack of drug efficacy in clinical trials. Because human motor neurons allow investigators to test drugs in the exact cell type that exists in people, iPSCs are a critical resource for understanding the disease and testing therapeutics.
Since 2016, Target ALS has provided iPSCs to the global research community through our Stem Cell Core. For a nominal fee and no intellectual property or data sharing restrictions, we provide access to a suite of iPSCs made from people diagnosed with ALS and healthy individuals. These iPSCs came from individuals with both familial and sporadic ALS, so various genetic mutations and backgrounds that can cause ALS are represented. Starting this year, Target ALS is embarking upon a vast expansion of this Research Core, in response to the needs of the worldwide ALS research community.
Experimental model systems using iPSCs are an important part of ALS research efforts but have been plagued with difficulty in reproducing results across research laboratories due to complicated protocols for generating disease-relevant cells and the large impact of genetic variation on experimental outcomes. We have assembled an international consortium of iPSC experts to solve these problems and provide robust ALS iPSC resources globally. New iPSC lines will be created from skin cells donated by patients carrying one of the following more commonly identified genetic mutations that cause ALS – C9orf72, FUS, SOD1, and TARDBP (TDP-43). The patient lines will be compared to a perfect “isogenic” control, equivalent to the mutant line with just the singular replacement of the mutant with the healthy gene. These iPSCs, cell type generation protocols, and data will all be shared worldwide as part of the Target ALS Stem Cell Core. This new resource will significantly remove barriers for academic and industry labs to access high-quality research tools to study ALS.
By continuing to support radically collaborative efforts that break down barriers to ALS research, we will realize a world where Everyone Lives.
The Stem Cell Core Consortium includes the following researchers:
Sami Barmada, MD, PhD, University of Michigan
RNA and protein biology expert and identification and characterization of genetic modifiers, 2D iPSC-derived cell culture
Johnathan Cooper-Knock, PhD, University of Sheffield
Identification and characterization of genetic modifiers, 2D iPSC-derived cell culture
Eran Hornstein, PhD, Weizmann Institute
Machine learning-driven high content iPSC imaging, 2D iPSC-derived cell culture
Jimena Andersen, PhD, Emory University
Organoid/assembloid differentiations (3D iPSC-derived cell culture)
Joao Duarte Tavares de Silva Pereira, PhD, Yale University
Organoid/assembloid differentiations and machine learning-driven high content iPSC imaging
Stem cell creation will be carried out by:
Bill Skarnes, PhD, The Jackson Laboratory
Barbara Corneo, PhD, Columbia University