24 - Amyotrophic Lateral Sclerosis

Summary

This chapter discusses preclinical disease models, biomarkers, clinical trial design options, and challenges to the conduct of Amyotrophic Lateral Sclerosis (ALS) clinical trials. The primary goals of most clinical trials in ALS are to slow disease progression as measured either by function or survival. Functional scales include measures of strength, pulmonary function, and a questionnaire called the ALS functional rating scale-revised (ALSFRS-R). The incidence of ALS is approximately 2/100,000/year. Fifty percent of people with ALS die within 3 years of onset of symptoms and 90% die within 5 years. The statistical techniques used in ALS clinical trials depend on the outcome measure. The largest challenge in clinical trials that use ALSFRS-R or other longitudinal outcomes measures is missing data. Development of a sensitive and specific diagnostic biomarker for ALS can help early accurate diagnosis and enrollment in clinical trials, which allows earlier initiation of potential therapies.