Access for All in ALS (ALL ALS) West Clinical Coordinating Center

Abstract Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, ultimately fatal, neurodegenerative disease with approximately 32,000 cases in the United States (US). With an estimated lifetime risk of 1/400, an average of 5,000 new US cases are diagnosed every year. A public private partnership (PPP) can be leveraged to rapidly advance regulatory science and scientific research

to support and accelerate the development of effective, new drugs to extend life for people living with ALS. Given the numerous failures in translating laboratory results into clinically effective therapies, the generation of high quality, diverse and longitudinal patient-derived biosamples and resulting downstream data is critical for our success. To this aim, our proposed ALS Clinical

Research Coordinating Center (ALSynCC) builds and expands upon the ongoing success of our Target ALS Natural History study and consortium and will include five sample/data repositories linked to detailed clinical information: 1) a biofluid repository that contains cross-sectional and longitudinal biofluid sample from asymptomatic and symptomatic patients where samples are

linked to detailed clinical information, whole genome sequencing, at-home measures of speech and respiratory function, 2) a longitudinal study of asymptomatic mutation carriers called the PREVENT study that will be expanded to include participants across the country, 3) an MRI- based neuroimaging repository to be newly implemented, 4) at-home measures of speech and

respiratory function, and 5) a large, well-annotated post-mortem tissue biobank containing brain, spinal cord and muscle tissue from patients. Each of these repositories is led by highly trained physicians and scientists, experts in the field. This use of multi-modal and multi-compartment sampling from each patient is a powerful method to characterize disease processes and will

improve translation of diagnostics, therapies, and outcome measures to the clinic. These highly curated biosamples and data resources are de-identified, linked to detailed clinical information, and will be made immediately available to the research community through the Consortium data portal. Our Target ALS natural history program is a successful public-private partnership between

academic and industry leaders and closely mirrors the overall goals of the proposed ALS Clinical Research Consortium and functions of the Coordinating Center (CC). A unique aspect of our model is to collect data and samples from asymptomatic individuals at risk for ALS, as well as from symptom onset to autopsy to provide a comprehensive sample and dataset for future

research studies. We will utilize our knowledge and tremendous success to expand on this existing infrastructure to maximize ALS patient enrollment in a highly synchronized research platform called ALSync that is administered by the ALSynCC. This nationwide ALSync network will work closely with NIH and other partners to coordinate and bridge ALS research and clinical

care across the country to: a) ensure inclusion of male and female patients of all racial and ethnic backgrounds, b) to improve access to clinical research and trials, c) to generate high quality patient samples and data, and d) to efficiently share data and analysis tools to accelerate research in the broader ALS community.