Blood Test Identifies People With ALS

By Will Boggs MD

July 28, 2020

NEW YORK (Reuters Health) - A panel of eight micro RNA (miRNA) can identify patients with amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND), researchers report.

"By sequencing micro RNA from brain exosomes we discovered a unique genetic fingerprint for ALS," Dr. Paul Alan Cox of the Institute for Ethnomedicine, in Jackson, Wyoming, told Reuters Health by email. "We can now with confidence distinguish blood samples of ALS patients from healthy people."

Currently, there is no standard biomarker for ALS/MND, although several potential biomarkers have been investigated, including miRNA.

Dr. Cox and colleagues examined whether miRNA sequences from enriched extracellular vesicles in blood plasma could consistently and significantly differentiate ALS/MND patients from healthy controls.

They used cell-specific protein markers to isolate a neural-enriched subpopulation of extracellular vesicles from plasma samples and compared miRNA content between healthy controls and patients with ALS/MND in two separate cohorts.

Analysis of samples from 10 healthy controls and 10 ALS/MND patients identified 101 differentially expressed miRNA, and after relative quantification of 34 of these miRNA, a panel of eight miRNA was found to differentiate controls from patients in both cohorts.

The precise disease-related associations between the miRNA identified in this study and their biological targets remain unclear, the researchers report in Open Biology.

Dr. Cox said that the potential benefits of this discovery could include early diagnosis, definitive diagnosis, earlier treatment, and the possible discovery of drugs that might be useful for treating ALS/MND.

"Currently, brain exosome extraction is a time-consuming and highly technical process," he said. "To be made available to patients, our discovery has to become a rapid, high-throughput diagnostic test approved by the" U.S. Food and Drug Administration.

"I think our laboratory approach can be translated by the pharmaceutical industry into a rapid, high-throughput blood assay that physicians could order," Dr. Cox said. "Such a test might be useful for patients at the first sign of possible symptoms of motor neuron disease, for individuals deemed at higher risk of ALS due to their family background or previous exposures to environmental toxins, or perhaps for older patients at certain age-related milestones, similar to the current guidelines for colonoscopies. Even for neurologists specializing in ALS, a rapid assay that can confirm a clinical diagnosis would be very useful."

Dr. Andres Trostchansky of Universidad de la Republica, in Montevideo, Uruguay, who recently reviewed lipid biomarkers for ALS, told Reuters Health by email, "The detection of biomarkers for the predisposition, onset, and progression of the disease is one of the most challenging issues in biomedicine. (The authors') finding is important to develop diagnostic and therapeutic strategies to improve the quality of life and life expectancy of patients."

"These results will aid in the early diagnosis of ALS/MND in humans using blood samples," he said. "Since there is no cure for the disease, early detection of the disease allows early intervention to improve the quality of life of patients."

The study had no funding, but Dr. Cox's lab is filing a patent on the use of the new biomarker.

SOURCE: Open Biology, online June 24, 2020.