Micro-RNA Levels May Be Diagnostic Marker, Distinguishing MS from Other Neurological Diseases
Patients with multiple sclerosis (MS) have higher levels of a micro-RNA called miR-150 in their cerebrospinal fluid, a liquid surrounding and protecting the brain and spinal cord. The study, validating the finding in some 600 people, suggests that miR-150 might be a marker for MS, distinguishing the disease from other neurological conditions.
Micro-RNAs are short stretches of RNA that control the activity of genes. A study from Karolinska Institutet in Sweden, titled “Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis,” used a three-step process to identify micro-RNAs that might differ between patients with MS and those with other neurological conditions, both inflammatory and noninflammatory. The report was published in the journal Neuroimmunology & Neuroinflammation.
In the first step, the team enrolled 15 patients with clinically isolated syndrome who had experienced an episode of MS-like neurological symptoms but did not yet have a definitive diagnosis, and 15 MS patients with relapsing disease. As a control group, 13 people with noninflammatory — and 14 with inflammatory — neurological diseases were also enrolled.
Researchers found 15 micro-RNAs that differed between patients and controls in the first group, and went on to validate the findings in a second, larger group of 142 individuals. In this group, the team also found that levels of the micro-RNA miR-145 and miR-150 were higher in MS patients compared to people with non-inflammatory neurological diseases.
Again scaling up, the researchers observed that, among a new 430-person cohort, only levels of miR-150 were different between groups. This particular micro-RNA was in higher concentrations in MS patients than in people with both inflammatory and non-inflammatory neurological conditions. Clinically isolated syndrome patients also had elevated levels compared to those with non-inflammatory neurological disease.
What’s more, those clinically isolated syndrome patients who soon would be diagnosed with MS had higher levels than those who had not progressed to MS by a second visit, and patients having oligoclonal bands — indicating the presence of antibodies — also had higher miR-150 levels than those without these bands.
The factor did not seem to be linked to relapses, number of brain lesions, or disability scores. But in patients treated with the antibody natalizumab (Tysabri), miR-150 levels were also higher relative to other MS patients.
Homing in on this group, the team noted that 12 months of natalizumab treatment lowered the levels of miR-150 in the cerebrospinal fluid, while increasing levels in blood plasma. Given that scientists believe natalizumab exerts its effect in MS by preventing immune cells from reaching the brain, researchers concluded that such cells were a likely source of miR-150. This hypothesis was supported by other findings, showing that miR-150 levels were linked to the presence of other immune and inflammatory cells and markers.
“Our findings demonstrate miR-150 as a putative novel biomarker of inflammatory active disease with the potential to be used for early diagnosis of MS,” the research team concluded.