PREVENT ALS: a multi-site longitudinal study of at-risk ALS mutation carriers

By the time weakness from amyotrophic lateral sclerosis (ALS) is evident, an estimated 30-50% of motor neurons have already degenerated, and the underlying disease biology is already firmly entrenched. Therefore, interventions that prevent pathological processes from beginning are more likely to succeed than those attempting to stop an already unfolding process. Preventative efforts are easiest to envision in individuals who carry highly causative mutations in known ALS genes. Based on family studies of other autosomal dominant neurodegenerative diseases, we estimate that there are 7,000 such mutation carriers in the U.S. alone. To make preventing ALS a reality for these genetically at-risk individuals, the field needs to define the earliest stages of the disease, identify/validate increasingly sensitive biomarkers of impending motor neuron loss and create cohorts of fully characterized ALS gene carriers that are clinical-trial ready the moment preventative therapies are available to test. To address each of these needs, two independent studies (DIALS and ALS Families Project) are joining forces to build a shared study called PREVENT ALS. With this proposal, we will build on the shared infrastructure and cohort of PREVENT ALS to 1) harmonize the clinical assessments and biosample methods of the two studies; 2) develop shared infrastructure; and 3) increase new participant enrollments, enhance follow-up visits for existing participants and establish a scalable framework for the expansion to other sites.?