New blood-based biomarkers can predict the emergence of Amyotrophic Lateral Sclerosis (ALS) symptoms months to years in advance, offering a crucial tool for preventative trials. Researchers from the National Institutes of Health (NIH)-funded Pre-symptomatic Familial ALS (Pre-fALS) study identified a panel of 19 proteins whose shifting levels may indicate when clinically manifest ALS will appear.
This discovery could enable interventions with preventative therapies before irreversible motor neuron damage occurs. Dr. Michael Benatar, senior author and professor of neurology and public health sciences at the University of Miami, said, “These biomarkers give us a far better idea of the timing, allowing us to estimate the time to symptom onset with an average error of about 18 months. That’s something we can work with.”
The Pre-fALS study, ongoing for nearly 20 years, collects data from individuals at high genetic risk for ALS but who are not yet symptomatic. Using high-throughput proteomic analysis on plasma samples from 137 participants, the team identified 92 proteins with differing levels before symptom onset. Machine-learning techniques refined this to a 19-protein panel, including neurofilament light chain (NfL), which maximized predictive accuracy for symptom onset within six months to five years.
Similar predictive results were achieved using data from the UK Biobank, suggesting broader relevance beyond the genetically predisposed Pre-fALS cohort. Amy Bany Adams, Ph.D., acting director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS), emphasized, “With preventative gene-targeting treatments now becoming available, there is a particularly urgent need for reliable biofluid-based signatures that indicate near-term onset in individuals that carry ALS risk genes.”
The drug Tofersen, already approved for symptomatic ALS, is currently being evaluated in the ATLAS clinical trial as a preventative therapeutic for pre-symptomatic ALS. This trial, designed by Dr. Benatar, aims to determine if early treatment can delay or avert the disease's onset.