Abstract

Biomarker Developments in Amyotrophic Lateral Sclerosis

Martin Turner, Professor/Consultant Neurologist, Oxford University

Multiple candidate neuroimaging and neurochemical biomarkers are emerging for the devastating adult-onset neurodegenerative disorder amyotrophic lateral sclerosis (ALS, also known as motor neurone disease). ALS overlaps with frontotemporal dementia clinically (through a dysexecutive and behavioural syndrome), neuropathologically (through cytoplasmic inclusions of TDP-43), and genetically (particularly G4C2 expansions in C9orf72). Biomarkers are required to improve patient stratification in ALS, as well as disease activity monitoring. This will improve therapeutic trial design, including faster no-go decisions, and also provide new mechanistic insights and drug targets. Multivariate, cross-platform modelling, and big data approaches involving machine-learning are emerging research fronts, and international collaborative efforts are addressing issues of standardization and harmonization. The study of pre-symptomatic carriers of genetic mutations linked to ALS, with a broader understanding of the risk factors in non-hereditary disease, is an important new initiative towards the long-term vision of primary prevention.