Researchers describe a small molecule involved in remyelination that could help distinguish between disease stages and predict disability
Multiple sclerosis is characterized by two different phenomena: demyelination (loss of myelin) predominates in the relapsing-remitting form, while neurodegeneration (damage and/or loss of nerve cells), although occurring early in the disease, becomes more prominent in the progressive form of MS. The regenerative protein neural adhesion molecule (NCAM) is known to play a crucial role in repairing damage to the central nervous system, and abnormalities in NCAM function have been associated with impaired myelination and the progression of disability in MS. However, the way in which NCAM is regulated during the different stages of MS remains unclear.
One molecule that targets and affects the function of NCAM is called micro ribonucleic acid (miRNA)-572. In people living with MS, the levels of miRNA-572 circulating in the blood are abnormally regulated, which lead to the hypothesis that miRNA-572, through its effect on NCAM, can impact the body’s ability to regenerate and repair nerve damage. A team of researchers from the Don C. Gnocchi Foundation and the University of Milano in Italy analyzed miRNA-572 in people living with different types of MS in order to determine if levels in the blood were correlated with progression and clinical characteristics of the disease. Their findings were published in the Journal of Translational Medicine.
The researchers measured the amount of miRNA-572 present in the blood of 62 participants with MS and 15 healthy volunteers without MS (control group). Within the MS group, 31 volunteers had relapsing-remitting MS, 15 had secondary progressive MS, and 16 had primary progressive MS. Levels of miRNA-572 were compared between MS and control participant groups, and also between the different forms of MS.
The researchers further compared miRNA-572 levels with degree of disability (assessed using the Expanded Disability Status Scale) in all MS participants.
In people living with MS, blood levels of miRNA-572 were highest in those with secondary progressive and relapsing remitting MS during the relapse phase, and lowest in those with primary progressive and relapsing remitting MS during the remission phase. The researchers also observed a link between miRNA-572 levels and degree of disability within the MS participant group as a whole: those with higher amounts of miRNA-572 were also more likely to have higher disability scores. An unexpected finding was that people living with MS had lower blood levels of miRNA-572 compared to non-MS participants.
The findings from this study reveal the potential of miRNA-572 as a non-invasive biomarker for distinguishing between different stages of MS and, by extension, for gauging the extent of remyelination associated with those stages. By measuring levels of miRNA-572 in the blood, the researchers were able to differentiate between the two progressive forms of MS – secondary (higher levels) and primary (lower levels) – as well as between the two stages in relapsing remitting MS – relapsing (high) and remitting (low). Healthy individuals without MS had higher blood levels of miRNA-572 than participants living with MS, which was surprising given that periods of MS remission were associated with lower levels overall.
miRNA-572 was also predicted to disable the production of the regenerative protein NCAM; as miRNA-572 levels go up, NCAM activity must go down. As a result, an individual with lower amounts of circulating miRNA-572 would be expected to have increased NCAM-driven regeneration and repair in the brain and spinal cord.
This work, while preliminary, is a first step in better understanding how regenerative molecules, such as NCAM, are potentially regulated by small, circulating microRNAs in MS. The authors propose that future work will involve experimentally validating the interaction and modulation of NCAM by miRNA-572 and confirming the initial findings in a larger group of participants.
Mancuso R et al. (2015). MicroRNA-572 expression in multiple sclerosis patients with different patterns of clinical progression. Journal of Translational Medicine. 13:148.