Current and emerging ALS biomarkers: utility and potential in clinical trials

ABSTRACT

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder which results in progressive muscle weakness as a prominent feature. However, clinical and pathogenic heterogeneity with regard to anatomical sites of disease onset and progression overtime are important features of the disease which have frustrated attempts to inform patients about their prognosis as well as limited the potential successes of therapeutic studies.

Areas covered: This article discusses: clinical biomarkers which can be measured by history, physical examination, and clinical scales of disability; genetic markers of ALS that may help to distinguish various ALS subtypes; fluid-based biomarkers are actively being pursued for their utility in understanding disease progression and prognosis; electrophysiological studies that are now widely used in ALS clinical trials; neuroimaging biomarkers whose development has been accelerated with evolving techniques.

Expert commentary: The investigation and development of biomarkers that could aid in diagnosis of ALS at earlier time points, prognostic biomarkers that could inform about the natural history of these heterogeneous presentations, predictive biomarkers aiding in understanding a potential response to therapy, and pharmacodynamic biomarkers to assess target engagement arguably represent the most important goals for improving ALS care and advancing ALS therapeutics.

KEYWORDS:

• Amyotrophic lateral sclerosis
• diagnosis
• prognosis
• pharmacodynamics
• neurofilament
• electrophysiology
• imaging

Declaration of interest

N Maragakis is site principal investigator in a study of Acthar gel in ALS (Mallinkrodt) and BIIB067 (Biogen/Idec), is a consultant for Above and Beyond NB LCC, and has served on the scientific advisory board for Orion Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This article was not funded.