Guiding Principles for Drug Discovery in ALS

This white paper outlines guiding principles for drug discovery and development in amyotrophic lateral sclerosis (ALS). It discusses the increasing global research activity focused on ALS, which has led to the identification of genetic risk factors and potential drug targets. Despite these advancements, ALS remains a progressive and fatal disease with limited treatment options. The document presents insights from workshops involving experts from various sectors, including academia and industry, which were further refined through a Delphi survey. It addresses the barriers to translating basic science into effective therapies and suggests principles aimed at improving the design of clinical trials for novel therapeutics. The paper emphasizes the need for an evidence-based approach to preclinical studies and the importance of optimizing drug discovery efforts to enhance the likelihood of successful clinical outcomes. Additionally, it reviews factors contributing to high failure rates in ALS clinical trials and provides recommendations for improving preclinical models and study designs.