MicroRNA Blood Test for Early ALS Diagnosis Seen as Feasible in Clinic

Study Finds 5 miRNAs in Readily Collected, Stored Blood Samples Identify Patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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ALS diagnosis | ALS News Today | diagnostic microRNA blood test | illustration of blood work in lab

The levels of five small RNA molecules, called microRNAs, inside tiny vesicles in the blood of people with amyotrophic lateral sclerosis (ALS) differ significantly from those of people without ALS and may offer a way of accurately and quickly diagnosing the disease, a study suggests.

Importantly, its researchers evaluated blood samples collected from across the U.S. and stored under different and non-stringent conditions, indicating that this blood test may be easily incorporated into everyday clinical practice for diagnosing suspected cases.

“Apparently, the extracellular vesicles shed into the blood protect their … cargo against differing environmental conditions,” said Paul Cox, PhD, the study’s senior author at Brain Chemistry Labs, a nonprofit research institute in Wyoming, said in an institute press release.

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Larger studies are needed to confirm these findings and further determine the biomarker potential of these microRNAs, the scientists added.

The study, “miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis,” was published in the Journal of the Neurological Sciences.

Diagnostic delays of about one year are common for people with ALS, and an “incorrect diagnosis occurs in 13–68% of cases,” the researchers noted.  Both contribute to poorer outcomes for patients, because proper care cannot be initiated until the correct diagnosis is confirmed.

“The need for better ALS diagnostic tools is readily apparent in the real-time challenges faced by ALS patients and clinicians,” the researchers wrote.

microRNAs carry genetic material, may allow faster ALS diagnosis

In a 2020 study, Cox’s team found that the levels of eight microRNAs inside extracellular vesicles in the blood were significantly and consistently different between ALS patients and healthy people.

microRNAs, or miRNAs, are small RNA molecules that regulate gene activity within cells. Extracellular vesicles (EVs) are tiny molecule-filled, sac-like structures naturally produced by various cell types to communicate with other cells.

Their findings suggested that these molecules, which include genetic material like RNA and DNA, could serve as diagnostic biomarkers for ALS.

However, the work was done using blood samples taken during a clinical trial, meaning they were collected and stored under stringent conditions not likely to be found in a typical practice.

“If a biomarker is to be developed for standard clinical use, it must be reproducible in different labs across time from samples collected by different investigators using different collection and storage protocols,” the researchers wrote.

With this in mind, the same team analyzed 100 blood samples — 50 from ALS patients enrolled in the National ALS Biorepository and 50 from people without the disease as a control group. All samples were collected from across the U.S. and stored under conditions more applicable to day-to-day clinical practice.

“None of the patients reported parents, brothers, sisters, or children with ALS suggesting that the majority of these cases were sporadic ALS,” the team wrote.

Among the eight previously identified microRNAs, five of them —miRNA-4454, miRNA-151a-5p, miRNA-146a-5p, miRNA-10b-5p, and miRNA-29b-3p — were found to be significantly altered in ALS patients relative to controls.

Three — miRNA-4454, miRNA-10b-5p, and miRNA-29b-3p — were significantly reduced in people with ALS, while the remaining two, miRNA-151a-5p and miRNA-146a-5p, were significantly increased.

Notably, similar changes in miRNA-4454 and miRNA-146a-5p had been previously reported in other ALS studies of human body fluids, outside EVs, further supporting their potential as ALS biomarkers.

The other three microRNAs trended toward differences similar to those seen in the prior study, but these failed to reach statistical significance.

“These five different miRNAs represent a robust ALS fingerprint worthy of further investigation for clinical use,” the scientists wrote.

“We were surprised that the microRNA test worked for samples collected from a variety of investigators under differing conditions,” said Sandra Banack, PhD, the study’s first author and a senior scientist at Brain Chemistry Labs.

The scientists noted a need for further research that includes validating these results in larger sample sizes and assessing how these EV-derived microRNAs relate to patient outcomes.

“Ideally, we would like to be able to correlate symptom onset, symptom duration, genetics, disease progression, and the prognostic and diagnostic potential of the miRNAs identified,” the researchers wrote.

While more work is needed for clinic use of EV-derived microRNA testing, the researchers stressed that these findings show it to be “robust and repeatable creating the background necessary to recommend further research in this area.”

The team is now further validating the blood test and has applied for a patent on the test. In the future, the researchers hope to partner with a diagnostic firm to develop the test for commercial use.