Scientists validate blood test that may speed up diagnosis of ALS
Biomarker test could be widely available within 2 years, scientists say
Blood levels of eight small molecules called microRNAs can accurately distinguish people with amyotrophic lateral sclerosis (ALS) from healthy people or those with other neurodegenerative diseases, a study shows.
Its developers believe this so-called “ALS fingerprint,” which has now been validated in multiple groups of people and in different laboratories, can be used as a disease biomarker along with other clinical tests to help speed up the process of reaching an ALS diagnosis.
“Faster diagnoses will allow for earlier treatment, which will improve patient outcomes,” Sandra Banack, PhD, the study’s first author from the Brain Chemistry Labs (BCL), a nonprofit research institution in Jackson, Wyoming, said in a BCL news story.
Paul Cox, PhD, the study’s senior author and BCL’s executive director, has plans to establish a diagnostic company partnership and to make this blood biomarker test available to neurologists within the next 1.5 to two years. BCL has already applied to patent the use of the biomarker.
The study, “A microRNA diagnostic biomarker for amyotrophic lateral sclerosis,” was published in Brain Communications.
No current definitive diagnostic test for ALS; misdiagnoses common
No definitive diagnostic test is available for ALS, a rare, fast-progressing neurodegenerative disease. Establishing such a diagnosis usually relies on an observation period during which doctors track the progression of symptoms and work to rule out other neurodegenerative conditions.
That diagnostic process can take months, sometimes more than a year, and even then, misdiagnoses are common. This means many people with ALS deteriorate significantly before they’re accurately diagnosed and can start treatment.
Therefore, there’s been a push to identify biomarkers, such as proteins or other molecules that are found at different levels in ALS, that can identify the likely presence of the disease through a simple blood or urine test.
Cox’s team has been focused on identifying an ALS fingerprint based on microRNAs (miRNAs), a type of small molecule that regulates gene activity, within extracellular vesicles (EVs) mostly derived from nerve cells. EVs are tiny particles secreted by cells that carry cargo, including miRNAs, proteins, and other materials to facilitate cell-to-cell communication.
The team previously discovered that blood levels of eight miRNAs derived from nerve cell-enriched EVs were consistently different between ALS patients enrolled in a clinical trial and people who did not have ALS. The findings were generally confirmed in a later study involving samples from a broader ALS patient population.
New study set out to validate miRNAs as ALS biomarker in additional group
In the new study, the researchers sought to further validate the use of these miRNAs as an ALS biomarker in an additional group of people.
The analysis involved blood samples from 119 ALS patients, 42 people with primary lateral sclerosis (PLS), 20 with Parkinson’s disease, and 150 healthy people. PLS is a neurodegenerative disease that has strong clinical overlap with ALS and was included as an ALS mimic, while Parkinson’s was included as a neurodegenerative disease control.
Results showed blood levels of all eight of the miRNAs — miR-199a-3p, miR-4454, miR10b-5p, miR-151a-5p, miR-199a-5p, miR-151a-3p, miR146a-5p and miR-29b-3p — significantly differed between ALS patients and healthy people. Five were found at higher levels in the ALS group, and three were found at lower levels.
The data “indicated identical fold regulation direction with similar magnitude to those found in prior published studies,” the researchers wrote.
Moreover, all eight miRNAs were found at significantly different levels between ALS patients and PLS patients, while five of the miRNAs were significantly different between the ALS and Parkinson’s groups.
Test could distinguish ALS from healthy controls with accuracy of up to 98%
Overall, the researchers found that measuring blood levels of these eight miRNAs could distinguish, with an accuracy of up to 98%, ALS patients from healthy controls.
With the results of this study and the previous ones taken collectively, this ALS fingerprint has consistently been able to distinguish the neurodegenerative condition across patient groups, laboratories, and sample collection methods, providing the researchers confidence that it could be a good and reliable disease biomarker in the clinic.
Ultimately, the scientists hope the blood test, used along with standard clinical assessments, could help doctors diagnose ALS faster.
“We envision this biomarker as a quick secondary measure of disease diagnosis following a neurologist’s clinical evaluation,” the researchers wrote. “This miRNA fingerprint fills an unmet amyotrophic lateral sclerosis drug development and medical diagnostic need and could facilitate the identification of amyotrophic lateral sclerosis at its earliest stages, thereby reducing diagnostic uncertainty.”
Another potential application of ALS blood biomarkers is for monitoring disease progression and treatment responses in clinical trials. It remains to be seen whether this biomarker is useful for that purpose, the team noted.
The exact relationship between each of the eight miRNAs and ALS is not entirely clear, but they’re involved in a wide range of disease-relevant biological processes, the researchers wrote.
“Further research identifying the disease-related pathways involved is warranted,” they added.
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