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One Simple Test May Detect ALS Years Before It Starts
0 Share Newsweek is a Trust Project member See more of our trusted coverage when you search. Prefer Newsweek on Google to see more of our trusted coverage when you search. A discovery in the blood could bring researchers one step closer to a long-sought goal in the fight against amyotrophic lateral sclerosis (ALS).
Scientists have identified a group of proteins that begin to change months—or even years—before symptoms of the neurodegenerative disease appear, raising hopes that people at risk could one day be treated before irreversible nerve damage occurs.
ALS, also known as Lou Gehrig's disease, is a progressive motor neuron disease that affects the nerve cells responsible for controlling movement. According to the Centers for Disease Control and Prevention ( CDC ), around 5,000 people in the United States are diagnosed with ALS each year.
Symptoms typically begin with painless muscle weakness, twitching and slurred speech, before gradually worsening to affect movement, swallowing and breathing.
The findings come from researchers analyzing data from the National Institutes of Health-funded Pre-symptomatic Familial ALS (Pre-fALS) study, which has followed people with a high genetic risk of ALS for nearly two decades.
Researchers examined plasma samples from 137 participants in the Pre-fALS study, including 33 people who later developed clinical signs of ALS or frontotemporal dementia .
Using a proteomic analysis technique known as Olink, the team measured levels of more than 5,000 proteins in the blood. They identified 92 proteins whose levels differed before participants went on to develop symptoms.
The researchers then used machine-learning models to determine which proteins provided the most accurate predictions of future disease onset.
They ultimately narrowed the list to a panel of 19 proteins, including neurofilament light chain (NfL), a protein found in nerve cells that previous research had shown rises in the blood shortly before ALS symptoms begin.
With information from these 19 proteins, the researchers were able to estimate when people would begin showing signs of disease with an average error of about 18 months. The models were effective across prediction windows ranging from six months to five years before symptom onset.
"If someone carrying an ALS-associated genetic variant had asked me in the past when they would become symptomatic, I would have struggled to provide a reasonable estimate," Benatar 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 ability to predict when symptoms may emerge could be particularly valuable as researchers test therapies designed to delay or prevent the disease before it becomes clinically apparent.
The study's findings were also replicated using data from the UK Biobank, suggesting the biomarkers may have relevance beyond people with inherited forms of ALS.
According to Amy Bany Adams, acting director of the NIH's National Institute of Neurological Disorders and Stroke, the research arrives at a pivotal moment for ALS treatment development.
"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," she said.
One such therapy is tofersen, a drug already approved for symptomatic ALS. It is currently being investigated in the ATLAS clinical trial to determine whether starting treatment before symptoms emerge can delay or even prevent the onset of the disease.
Benatar said the work would not have been possible without the participants who volunteered to take part in the study over many years.
"This is all possible because of the members of the carrier community who believe in our mission of preventing ALS and have supported and participated in our research," he said. "It has been one of my life's greatest privileges to give something back."
Ran, X., Wuu, J., Qin, Z.S. et al. Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS. Nat Med (2026). https://doi.org/10.1038/s41591-026-04528-x
Contact Newsweek editors on this story: Charlotte Nisbet and Sam Wilson .
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