A new study has identified a panel of 19 proteins in blood that could potentially detect Amyotrophic Lateral Sclerosis (ALS) up to five years before symptoms manifest, offering a potential pathway for earlier diagnosis and treatment.
Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder that damages nerve cells controlling voluntary muscle movement. The disease can rapidly impair a person's ability to walk, talk, swallow, and eventually breathe. Initial symptoms, such as subtle muscle twitches or speech difficulties, can be easily overlooked, often delaying diagnosis and the initiation of treatments that may help slow the disease's progression.
This new research, published in Nature Medicine, analyzed 20 years of blood samples from individuals at elevated genetic risk for ALS. Researchers identified nearly 100 proteins that showed altered levels prior to the onset of clinical symptoms. Utilizing machine learning, this list was narrowed down to a 19-protein signature, including neurofilament light chain.
"By studying blood samples from people at elevated genetic risk for ALS, we identified protein signatures that predict whether someone is going to phenoconvert in the relatively near future," said Dr. Michael Benatar, senior study author and executive director of the ALS Center at the University of Miami. "This could be an incredibly valuable tool for us to select appropriate people for inclusion in future ALS prevention trials and ultimately to develop effective treatments."
The developed blood panel was able to estimate the time of symptom onset with an average error of 18 months, with predictions ranging from six months to five years before symptoms appeared. The researchers are also exploring cerebrospinal fluid samples for additional protein markers.
The study's findings come at a time when the United States is experiencing an increase in ALS diagnoses. The national ALS Registry reported that approximately 33,000 Americans were living with the disease in 2022, a number projected to exceed 36,000 by the end of the decade. Approximately 90% of ALS cases are sporadic, meaning they occur without a clear family history, while about 10% are linked to genetic factors.
Currently, ALS is typically diagnosed through neurological examinations, nerve conduction studies, MRI scans, and analysis of cerebrospinal fluid. The development of this blood test is a significant step toward improving diagnostic accuracy and timing, which could be crucial for clinical trials aiming to test new therapies.
"Without these markers, it would be difficult to run a trial because we’d have no idea who would actually develop ALS or FTD and when," Benatar explained. "Because we can now predict when phenoconversion is likely, we have a much better sense of who to enroll, and we have a measurable way to know if a therapy is working."
It remains unclear when this potential blood test might be available to the public. The research is conducted in partnership with the ALS carrier community, who are committed to advancing the understanding and treatment of the disease.