University of Miami Researchers Develop Blood Panel to Predict ALS Onset

For families carrying genes linked to amyotrophic lateral sclerosis (ALS), the period before symptoms appear is often defined by a grueling uncertainty. While some carriers develop the disease young, others do so later in life, and some never do. Now, an international research team led by the University of Miami Miller School of Medicine has developed a tool to quantify that wait.

The team identified a specific signature of proteins in the blood that signals phenoconversion—the shift from being a genetic carrier to showing clinical symptoms. By tracking these biomarkers, researchers can now better predict who is likely to develop the disease in the near future, creating a critical window for potential intervention before permanent nerve damage occurs.

The 19-Protein Panel vs. NEFL

For years, the gold standard for pre-symptomatic ALS detection has been a single protein called neurofilament light chain (NEFL), which spikes when neurons are damaged. While NEFL remains the most useful individual protein, the new 19-protein panel outperforms it across almost every time frame tested.

The gap in performance remains evident even as the window widens.

One of the most surprising findings is that many of these 19 proteins are not markers of nerve damage. A significant portion are tied to muscle biology, including proteins involved in muscle structure and breakdown. This suggests that muscle-related changes may begin years earlier than previously understood, challenging the conventional view that the disease begins solely with the death of nerve cells.

Two Decades of Data from Pre-fALS

This breakthrough is the result of nearly 20 years of longitudinal research. This project tracked people with elevated genetic susceptibility to ALS and frontotemporal dementia (FTD) using neurological exams and blood draws.

For the primary analysis, the team examined 516 blood plasma samples from 137 participants. This group included 33 people who eventually developed ALS, 35 who already had the disease, 10 gene carriers who remained asymptomatic, and 59 healthy controls. Using a single platform, researchers measured over 5,400 proteins, eventually narrowing the list to 92 that changed in the blood before symptoms appeared. Machine learning was then used to isolate the most accurate 19-protein combination.

The researchers validated these results using information from the UK Biobank, which yielded similar findings. While the study is a major step forward, the team cautions that the test is not yet ready for clinical use. It requires further validation in larger, more diverse groups and the development of simpler, more widely available laboratory methods.

Implications for Prevention Trials and Tofersen

The ability to time the onset of symptoms is not just a matter of psychological relief; it is a clinical necessity for the next generation of treatments. New gene-targeting therapies, such as tofersen—which is already approved for some ALS patients—are currently being tested to see if they can delay or prevent the disease if administered before symptoms emerge.

The 19-protein panel could serve as a critical tool for enrolling the right participants in these trials at the exact moment they will benefit most.

By reducing the average error of onset estimation to about 18 months, the research provides a window that clinicians can actually utilize.