Image: A photomicrograph of a demyelinating multiple sclerosis lesion. Immunohistochemical CD68-staining highlights numerous macrophages (brown); original magnification 10x (Photo courtesy of Wikimedia).
Researchers have identified unique dysregulated microRNAs (miRNAs) from exosomes in the blood of Multiple Sclerosis (MS) patients. The findings could lead to development of a simple diagnostic blood test for this debilitating chronic neurologic disease.
Currently, there is no definitive test for MS. Diagnosis and disease monitoring relies on several parameters, including clinical examination, MRI, cerebrospinal fluid assessment, and electrophysiology. These tests are costly and still have limited utility to discriminate between different stages of the disease.
The study was led by researchers at University of Sydney (Sydney, Australia) and Royal Prince Alfred Hospital (Australia), and was made possible through the generosity of patients at Brain & Mind Centre’s multidisciplinary Multiple Sclerosis Clinic.
The team previously showed that some miRNAs are selectively packaged into exosomes for release from the cell. Exosomes circulate in blood and can be purified in the millions from a single vial of blood. They are released by healthy and diseased cells, circulate throughout the body, and can deliver cargo of information to multiple cells.
In inflammatory diseases such as MS, there is a significant increase in circulating exosome concentrations. Given that exosomes can cross the blood-brain barrier, it is likely that some of the circulating exosomes in MS patients come from affected central nervous system cells or the associated inflammatory milieu. The researchers hypothesized that physiological changes associated with MS and its progression is reflected in differences in serum exosomal miRNAs, so they investigated their utility as biomarkers of MS.
“In studying the blood exosomes of healthy volunteers and patients with MS, the research team identified a molecular signature of MS that not only correctly diagnoses MS, but also discriminates between patients with different stages of disease,” said Michael Buckland, of RPA Hospital and associate professor at University of Sydney. Using next-generation sequencing (NGS) and integrative bioinformatics they found that serum exosome miRNA profiles not only distinguish MS from healthy controls, but also distinguish between 2 MS subtypes: relapsing-remitting MS (RRMS) and progressive MS. The team identified 9 unique miRNA molecules that differentiate between these two subtypes. They validated 8 of the 9 miRNAs in an independent group of progressive MS cases, providing reproducibility of the findings.
“This is the first demonstration that miRNAs associated with circulating exosomes in blood are informative biomarkers not only for the diagnosis of MS, but in predicting disease subtypes with a high degree of accuracy,” said Prof. Buckland.
“This blood test may allow people with MS to begin treatment earlier, and identify the most appropriate treatment for their condition,” said Dr Matthew Miles, CEO MS Research Australia, which funded the research via an incubator grant, “This, in turn may lead to fewer relapses and a slower loss of brain volume, resulting in slowing or potentially halting progression of the disease for the person living with MS. It will also help remove the uncertainty surrounding which subtype of the disease an individual has and therefore be a catalyst for better outcomes.”
The study, by Ebrahimkhani S et al, was published October 31, 2017, in the journal Nature Scientific Reports.
University of Sydney
Royal Prince Alfred Hospital