Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects roughly 2 subjects per 100,000 in the United States; however, given the rapid decline and mortality, there are low prevalence rates. Although ALS is considered a single disease, it, in truth, probably represents a series of disorders with different clinical patterns and different pathophysiologic mechanisms that eventually coalesce into a single entity. The challenge has been to target these different pathophysiologic abnormalities, and so far, most drug studies have focused on only one or two different pathways. Over 50 well-designed clinical trials have been conducted in ALS over the last 25 years and with the exception of the Riluzole trial, all have failed.
Areas covered: In this review, the authors highlight some of the recently concluded, ongoing or planned Phase II and Phase III studies in ALS. Furthermore, they summarize the progress in the recently initiated stem-cell therapy trials in ALS.
Expert opinion: The challenge remains for developing effective targeted therapeutic interventions for ALS. However, with improved recognition of the complex interplay of several factors that may contribute to ALS pathogenesis, in addition to improved patient selection criteria, outcome measures and biomarkers for drug development, advancements may be made in the future.
Keywords: amyotrophic lateral sclerosis; clinical trials; motor neuron disease; stem-cell therapy.