The need for biomarkers in amyotrophic lateral sclerosis drug development

Recent contributions to Neurology® have highlighted the disappointing lack of demonstrated efficacy of novel therapeutic approaches to amyotrophic lateral sclerosis (ALS).^1–3 Failure of translation, from promising preclinical studies to positive clinical trials, has raised concerns about the relevance of animal models and about clinical trial design. Development of novel therapeutics in ALS is also severely hampered by the lack of a biologic marker (biomarker) defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to a therapeutic intervention.”⁴ The importance of biomarkers in therapy development is underscored by the fact that for diseases in which good biomarkers exist, such as glycosylated hemoglobin for diabetes and serum lipid profiles for atherosclerotic coronary artery disease, there are multiple approved drugs, while for diseases in which there are no good biomarkers, such as Alzheimer disease, muscular dystrophy, and ALS, there are very few therapeutic options. Biomarkers have been proposed for ALS, although none are currently incorporated into clinical …