Potential blood biomarker of Gilenya response found in MS patients

MicroRNA may help ID those without disease activity after treatment

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A microRNA called miR-548a-3p, a small molecule important for regulation of gene activity, may help to identify people with multiple sclerosis (MS) who will reach no evidence of disease activity — a status known as NEDA-3 — after treatment with Gilenya (fingolimod), a study found.

Data showed that levels of this molecule after six months of treatment were significantly higher in patients who ended up attaining NEDA-3 at 24 months, meaning they experienced no relapses, no MRI activity, and no disease progression over the two years of follow-up.

“Our study is the first one to identify miR-548a-3p as [a] treatment response biomarker in MS patients under [Gilenya] treatment,” the researchers wrote.

The study, “miRNA 548a-3p as biomarker of NEDA-3 at 2 years in multiple sclerosis patients treated with fingolimod,” was published in the Journal of Neuroinflammation.

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MS is caused by the immune system attacking the protective coating, called myelin, that surrounds nerve cells, leading to neuronal damage. A number of treatments can be used to dampen inflammation and slow the accumulation of disability in MS.

However, there are few methods available for clinicians to monitor how patients respond to the use of such therapies.

MRI scans remain the main tool used to monitor disease activity and treatment response, with more affordable and easy-to-obtain biomarkers being needed to improve patient monitoring.

microRNAs, or miRNA for short, are small stretches of genetic material that regulate gene activity, leading to an increase or decrease in the production of certain proteins within a cell. These molecules can be isolated from the blood and are stable when stored for extended periods, making them ideal candidates for biomarkers.

In this study, researchers at the Brigham and Women’s Hospital, in Boston, set out to identify circulating miRNAs that could serve as biomarkers of disease activity and progression in people taking Gilenya for MS.

The team was particularly interested in biomarkers that could predict NEDA-3 after two years of treatment.

Samples were examined from people with the neurodegenerative disorder who are participating in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital study. Dubbed CLIMB, the study follows MS patients with clinical examinations, MRI scans, and blood sampling conducted yearly. Here, participants had blood samples collected about six months after starting treatment with Gilenya.

A total of 53 relapsing-remitting MS (RRMS) patients, with a mean age of 42.2, were included in the study. About three-quarters (75.5%) were women. The participants had minimal to no disability, and had experienced, on average 0.6, relapses per year in the past two years.

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miRNA showed accuracy of over 88% in study

In a first analysis involving samples from 31 patients, researchers found 24 miRNAs that were significantly different in individuals with NEDA-3 compared with those who experienced evidence of disease activity — meaning relapses, new MRI activity, or disability progression — over the two years.

Of those, five miRNAs were chosen for validation in the remaining 22 patients, who were called the validation group. In this group, only levels of miR-548-3p remained significantly different in MS patients with sustained NEDA-3 at two years compared with those with evidence of disease activity.

The miRNA remained significantly increased after accounting for age, sex, and disability level before treatment initiation. The results showed an accuracy of 88.2% in distinguishing patients with NEDA from those with disease activity after two years.

According to the researchers, “these results provide a new tool for monitoring treatment response in clinical practice.”

As a whole, our study not only provides a new biomarker for treatment response in patients with MS under [Gilenya] treatment, but also opens the door for future research unraveling the functional role of miR-548a-3p in [Gilenya]-treated MS patients.

In computer analyses, the team identified 247 genes that were likely targets of miR-548a-3p. Some of those genes were related to the differentiation and function of lymphocytes, a type of white blood cells that helps the body fight infections and disease, but no changes in immune cells were identified in patients with NEDA-3.

“These results may point out that the source of circulating miR-548a-3p could not only be cells, but also micro-vesicles, exosomes, or apoptotic bodies in which miRNA is packaged,” the researchers wrote.

“As a whole, our study not only provides a new biomarker for treatment response in patients with MS under fingolimod treatment, but also opens the door for future research unraveling the functional role of miR-548a-3p in fingolimod-treated MS patients,” the team concluded.