Blood protein panel may offer new way to identify ALS, researchers report
Experimental approach achieved 98.3% balanced accuracy in validation group
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- ALS is a progressive neurological disease that damages and eventually kills the nerve cells that control movement.
- Diagnosing ALS can take about a year and involves evaluating symptoms and performing tests to rule out other conditions.
- An experimental panel of 10 blood proteins distinguished people with ALS from healthy controls with 98.3% balanced accuracy in a study.
A combination of 10 blood proteins distinguished people with amyotrophic lateral sclerosis (ALS) from healthy people with 98.3% balanced accuracy in a new study.
“This 10-protein combination in our ALS disease prediction model classified ALS vs control with superior accuracy … to previously published studies,” researchers wrote. However, the researchers noted the panel needs further testing before it can be used to help diagnose ALS.
The study, “Ten protein panel predicts ALS from plasma with high accuracy,” was published in Nature Communications. It was funded by Hop On A Cure, the American Brain Foundation, the ALS Association, the American Academy of Neurology, and the Muscular Dystrophy Association.
Why diagnosing ALS remains a challenge
ALS is a rare neurological disorder in which motor neurons, the nerve cells that control movement, gradually become damaged and die. Diagnosing ALS involves evaluating a person’s symptoms and performing tests to look for signs of the disease and rule out other conditions.
Getting an ALS diagnosis can take time. One study found that patients waited a median of 11.5 months from their first symptoms to a confirmed diagnosis. Some patients also receive an incorrect diagnosis before ALS is identified.
Researchers are working to make ALS easier to diagnose and improve diagnostic accuracy. One approach is to look for blood proteins that may help distinguish people with ALS from healthy people or those with other conditions.
A team at Emory University measured 323 proteins in blood samples from 632 people with ALS who received care at the university’s ALS center and 160 healthy people, mainly spouses and unrelated care partners at the same center. The researchers used NULISA, a technology developed by Alamar Biosciences that can detect very small amounts of many proteins in the blood at the same time.
“We built NULISA to measure low-abundance proteins in blood that other technologies struggle to see, and to measure many of them at once. This study shows why that matters,” Yuling Luo, PhD, founder, CEO and chair of Alamar, said in a company press release. “By profiling brain-derived and inflammatory proteins together, the Emory team identified a multi-protein signature that outperformed single marker testing.”
Researchers identify 10 blood proteins linked to ALS
The researchers initially found 84 blood proteins with statistically significant differences between people with ALS and healthy controls. Using computer-based analyses, they narrowed the candidates to 12 proteins, then selected 10 for the final panel.
Two proteins in the panel, neurofilament light chain (NfL) and neurofilament heavy chain (NEFH), are well-established markers of nerve damage in ALS. Two others, pTau-181 and VEGFA, have also been linked to ALS. The remaining six — FOLR1, TREM1, CALCA, NRGN, LAMP3, and PTX3 — had not previously been reported as ALS blood biomarkers.
“We saw the proteins we expected, like neurofilament and phosphorylated tau, but we also found differences in proteins that hadn’t been linked to ALS in blood before,” said Eleanor Varian Thomas, MD, assistant professor at Emory University School of Medicine and co-author of the study.
“Several of these new proteins may also tell us something about ALS biology itself, which we plan to explore as we test the protein signature in larger and more diverse patient groups,” Thomas added.
The researchers then tested the 10-protein panel in a separate group of 144 people with ALS and 37 healthy controls. The panel achieved 98.3% balanced accuracy, a measure that accounts for how well it correctly identifies both people with ALS and those without it.
Protein panel outperforms individual marker in identifying ALS
The 10-protein panel performed better than tests using NfL alone or smaller combinations of proteins. NfL alone achieved 89.9% balanced accuracy, compared with 98.3% for the full panel.
One limitation is that the researchers compared people with ALS only with healthy controls. In clinical practice, a blood test would also need to distinguish ALS from other neurological diseases that can cause similar symptoms.
The study also used blood samples collected at a single medical center. Further studies involving patients at multiple centers are needed to confirm the findings before the panel can be developed into a clinical test.
“The primary application of these data will be for the development of a focused biomarker panel for clinical use that can be applied in both general neurology and primary care settings, which will help to triage patients at high risk for ALS for further evaluation with expert clinicians,” the team concluded.
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