Specific MicroRNA Expression Changes According to the Multiple Sclerosis Disease Stage
Researchers at the Don C. Gnocchi Foundation and the University of Milano in Italy recently discovered that the levels of a specific RNA molecule vary in patients with multiple sclerosis (MS) according to their disease stage and clinical progression. The study was published in the Journal of Translational Medicine and is entitled “MicroRNA-572 expression in multiple sclerosis patients with different patterns of clinical progression.”
MS is a progressive neurodegenerative autoimmune disorder that results from an attack on the central nervous system by the body’s own immune system, causing inflammation and damage to the myelin layer that covers and protects nerve fibers. Myelin loss leads to impairment in signal transmission along the nerve fibers, affecting motor function (coordination, balance, speech and vision), causing irreversible neurological disability and paralysis. It is estimated that more than 2.3 million people in the world suffer from the disease.
Although demyelination and failure in re-myelination are typical features seen in MS patients, the factors that control these processes are still not clear. One protein called neural cell adhesion molecule (NCAM), which is known to be involved in the central nervous system reparative mechanism, has been suggested to play an important role in these processes. NCAM has been reported to be a possible target of a microRNA (miR, a small non-coding RNA molecule able to regulate gene expression) called miR-572, which was recently found to be deregulated in MS.
In the study, researchers evaluated the serum levels of miR-572 in a cohort of MS patients with different clinical forms to determine whether there is a possible correlation with disease progression and/or clinical features. In total, 77 participants were analyzed, 16 patients with primary progressive MS (PPMS), 15 with secondary progressive MS (SPMS), 31 with relapsing remitting MS (RRMS) and 15 matched healthy controls.
Researchers found that the expression of miR-572 was overall decreased in MS patients in comparison to the healthy controls. miR-572 was significantly increased in SPMS and in RRMS during disease relapse, while it was found to be decreased during inactive phases of RRMS and in PPMS. These findings led the team to suggest that miR-572 might be a valuable biomarker to discriminate between PPMS and SPMS, as well as between relapsing and remitting phases in RRMS.
The authors propose that high levels of miRNA-572 are most likely associated to a decrease in expression and activity of NCAM protein, and consequently of the central nervous system reparative mechanism, leading to an increase in demyeliniation typical of MS stages that are more progressive and debilitating.
From a patient’s perspective, these findings on MS pathogenesis and the regulation of the NCAM reparative protein are important as they may offer new therapeutic avenues against the disease, namely therapies aiming at re-myelination of the patient’s neurons to prevent their degeneration.