Researchers Develop a Potential Blood Test for Diagnosing ALS

UC Irvine researchers are part of an international team developing a new blood test to diagnose ALS and track its progression.

Irvine, Calif., June 23, 2026 — A “diagnosis of exclusion” is often how patients learn that they have Amyotrophic Lateral Sclerosis (ALS), the highly debilitating neurodegenerative disease that robs people of their ability to move and eventually breathe.

“It can be difficult to determine if a patient has ALS, because there is no radiology or lab test to diagnose it, so many other related conditions must be ruled out first,” says Albert La Spada, MD, PhD, a Distinguished Professor of Pathology and Neurology at the UC Irvine School of Medicine. This process of exclusion wastes valuable time for those suffering from ALS.

“The more quickly we can diagnose ALS, the sooner patients can enroll in clinical trials and potentially benefit from new therapies,” says La Spada. “Quicker diagnosis also allows for all necessary supportive and ancillary care to be put in place more quickly.”

Now, thanks to a team of researchers from UC Irvine; the University of Ulm, Germany; and the Mayo Clinic, a tool for faster diagnosis is on the horizon.

“We have developed a new blood test to facilitate the diagnosis of ALS,” says La Spada. “We can also potentially use this blood test to track the rate of disease progression.”

Their findings appear in a new paper published in the Journal of Clinical Investigation.

The Role of the Epigenome

As noted in the paper, emerging evidence suggests that epigenetic changes, accumulated over time due to environment and lifestyle factors, contribute to ALS pathogenesis and may influence disease progression.

The researchers tested this theory by studying epigenetic methylation signatures from cell-free DNA (cfDNA), which can now be isolated from blood samples.

By analyzing cfDNA, the researchers were able to detect differentially methylated genes, including several implicated in ALS disease risk and pathogenesis. Integrating multiple epigenetic features allowed them to delineate a distinct epigenetic signature.

An “ALS” Methylome Signature

Using this “methylation signature,” the researchers identified approximately 70% of patients with ALS with close to 100% specificity. They also identified a set of genes whose methylation status significantly correlated with clinical disease progression.

Their results reveal the potential of cfDNA-based biomarkers to accurately diagnose ALS.

“We can use this new type of DNA to develop a more powerful way to diagnose disease and track disease progression,” explains La Spada. “This new biomarker can facilitate the future development of new therapies to treat ALS patients.”

While the initial pilot study involved 20 patients with sporadic ALS, 10 with C9orf72 inherited ALS, 10 presymptomatic C9orf72 familial ALS carriers, and 21 non-disease control individuals, the researchers are now working to replicate their findings in a much larger population of 500 individuals.

This research is being supported by Target ALS and the ALS Network. It represents a collaboration between UC Irvine (led by La Spada, MD, and Wei Li, PhD), the University of Ulm, Germany (led by Sebastian Michels, MD), and the Mayo Clinic Jacksonville (led by Leonard Petrucelli and Mercedes Prudencio) in coordination with an industry partner (TWIST Biosciences). UC Irvine researchers Eric Arnold, PhD; Zhuoxing Wu, MD, PhD; Craig Bennett, PhD; and Leslie Thompson, PhD, were also involved in this work.

About the UC Irvine School of Medicine: Each year, the UC Irvine School of Medicine educates more than 500 medical students and over 180 PhD and MS students. Nearly 900 residents and fellows are trained at the UCI Medical Center and affiliated institutions. The School of Medicine offers multiple MD, PhD and MS degrees, and students are encouraged to pursue an expansive range of interests and options. The UC Irvine School of Medicine is accredited by the Liaison Committee on Medical Education and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.