MicroRNA in Multiple Sclerosis May Signify Disease Progression

RNA DNA molecules
RNA DNA molecules
Several microRNA were found to be associated with lesion volume and brain atrophy in multiple sclerosis.

Multiple microRNA serum samples from patients with multiple sclerosis (MS) correlated well with magnetic resonance imaging (MRI) studies used to measure disease activity, supporting their use as biomarkers for disease progression, according to a study published in JAMA Neurology.

Investigators led by Keren Regev, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, retroactively enrolled 120 patients from Brigham and Women’s Hospital who were participants in the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. The group was separated into 2 independent cohorts, according to the range of MRI images available: cohort 1 (n = 41) had only brain MRIs available, while cohort 2 (n = 79) had high-resolution imaging of the brain and spinal cord available.

When microRNAs detected in plasma were compared with MRI results, they showed associations that were both protective and pathologic for MS in both cohorts. Protective associations with disease progression were observed in 4 microRNAs (hsa.miR.142.5p, hsa.miR.143.3p, hsa.miR.181c.3p, and hsa.miR.181c.5p), while 2 (hsa.miR.486.5p and hsa.miR.92a.3p) were pathogenically associated with the ratio of T1 hypointense to T2 hyperintense lesion volumes in the brain, and another pair (hsa.miR.375 and hsa.miR.629.5p) was associated with brain atrophy.

In both cohorts, 7 microRNAs were identified (hsa.miR.19a.3p, hsa.miR.101.3p, hsa.miR.30e.5p, hsa.miR.19b.3p, hsa.miR.29c.3p, hsa.miR.32.5p,and hsa.miR.195.5p) were significantly associated with clinical disability (Expanded Disability Status Scale [EDSS] scores), with strongest associations with brain and spinal cord atrophy.

One of the more striking findings of the study was a specificity in the topographical location of different types of microRNA signatures identified, with little overlap between the types that corresponded to brain lesions measured by T2 lesion volumes and T1:T2 ratios compared with those associated with brain atrophy. These findings point strongly to differences in underlying mechanisms of focal lesions and neurodegenerative loss involved in MS, the investigators said.

In a related editorial,2 Darin T. Okuda, MD commented that “having markers specific for brain and spinal cord involvement would be of great significance to the management of patients with MS, especially if higher efficacy treatments could be initiated earlier in the disease course to reduce clinical disability.”

The investigators also identified several microRNAs that were associated with specific MRI outcomes, although these were not considered significant after correcting for comparative factors. This, they reported, suggests the need for further studies in MS and other neurodegenerative diseases to identify whether these findings are specific to MS.

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  1. Regev K, Healy BC, Khalid F, et al. Association between serum microRNAs and magnetic resonance imaging measures of multiple sclerosis severity [published online January 23, 2017]. JAMA Neurol. doi: 10.1001/jamaneurol.2016.5197
  2. Okuda DT. Are miRNAs appropriate biomarkers for radiologic measures of tissue injury in multiple sclerosis? [published online January 23, 2017]. JAMA Neurol. doi: 10.1001/jamaneurol.2016.5384