Answer ALS: Individualized Initiative for ALS Discovery

Exciting progress in Amyotrophic Lateral Sclerosis (ALS) in the last few years has been made with the identification of new genetic causes of this disease. In addition, induced pluripotent cells (iPSC), which are adult somatic cells reprogrammed to a pluripotent stem cell-like state, can be derived from ALS patients and subsequently differentiated into the affected neurons and glia. Since the discovery of the first ALS gene 25 years ago and the creation of the first ALS mouse model, much has been learned about the disease. Yet despite these discoveries and critical research tools, truly effective therapies and good biomarkers absolutely required to make progress have not been forthcoming. It is clear that single research labs and simple animal models are not sufficient in finding the root cause of ALS in the vast majority of patients, identifying subtypes of disease and defining the pathophysiological pathways and drug targets along with highly relevant biomarkers. Only a large scale, concerted, and coordinated collaborative effort will make a difference in a timely manner. The proposed plan will bring together investigators across many disciplines needed to tackle ALS: iPSC technologies, cell biology, drug screening, genomics, proteomics, clinical observation, big data and machine learning. Of note, there is tremendous clinical heterogeneity within ALS, and there are many clinical forms fruste of ALS, and closely related neurodegenerative motor neuron diseases. Because the pathological relationship of these diseases is uncertain, this study will include ALS and related motor neuron diseases (MND). By creating a very large repository of iPSC, bio-fluid samples, gene sequencing, and carefully collected clinical phenotype information, this project will have a transformative effect on the landscape of ALS research. Until now, individual ALS researchers have labored to use small datasets to shed light on this uncommon disease and attempted to develop targeted