Key Myelin Protein Shows Promise as Biomarker for MS

Myelin basic protein in certain extracellular vesicles at higher levels in patients

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An illustration of damaged myelin.

The tiny sacs of cellular content that are released by oligodendrocytes — the myelin-producing cells of the brain and spinal cord — may be good biomarkers for the diagnosis and prognosis of multiple sclerosis (MS) patients, a new study has found.

The research showed that levels of myelin basic protein (MBP), a key myelin protein, in these extracellular vesicles are significantly higher in MS patients than in healthy people. Also, patients with a primary progressive disease course have increased levels compared with those with relapsing forms of MS.

The findings also pointed to oligodendrocyte-derived extracellular vesicles as a possible means to measure disability levels in MS patients, but “it will be necessary to confirm these results in larger cohorts of patients,” researchers wrote.

The study, “Myelin Basic Protein in Oligodendrocyte-Derived Extracellular Vesicles as a Diagnostic and Prognostic Biomarker in Multiple Sclerosis: A Pilot Study,” was published in the International Journal of Molecular Sciences.

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Early and precise diagnosis of MS type helps determine appropriate treatment

MS is caused by the immune system attacking the myelin sheath, a fatty substance that covers nerve fibers and is essential for the rapid transmission of electrical signals between nerve cells.

The vast majority of MS patients (85%) are first diagnosed with relapsing-remitting MS (RRMS), a form of the disease in which relapses, or periods of symptom worsening, are interspersed by periods of remission where symptoms ease.

However, the disease is highly variable. About 15%–30% of these patients will eventually transition to a secondary progressive disease course, in which symptoms continue to progress over time even in the absence of relapses.

Also, the other 15% of patients initially present with PPMS, meaning their neurological function worsens continuously from symptom onset, without relapses or remissions. This MS type is difficult to diagnose and treat, and is associated with a poor prognosis.

A precise diagnosis of MS type in the initial stages of the disease is of major importance to determine treatment and rehabilitation decisions. Currently, a diagnosis is based on clinical, imaging, and laboratory information; however, easy and non-invasive biomarkers are not available.

MBP is one of the main myelin proteins and is a known target of erroneous immune responses in MS. This protein is produced by oligodendrocytes, the specialized cells responsible for making myelin in the brain and spinal cord.

A minimally invasive blood test measuring the concentration of MBP [myelin basic protein] in ODEVs [oligodendrocyte-derived extracellular vesicles] is a promising tool that could facilitate MS diagnosis.

Because oligodendrocytes release extracellular vesicles, tiny membrane-coated sacs containing proteins, fats, and genetic material from the original cell, that can reach the bloodstream, a team of researchers in Milan hypothesized that the amount of myelin proteins in these vesicles could help determine the diagnosis and prognosis of MS.

To find out, the researchers examined oligodendrocyte-derived extracellular vesicles (ODEV) isolated from the blood of 136 participants: seven with clinically isolated syndrome (CIS, a first episode of MS-like symptoms), 18 with PPMS, 49 with RRMS, and 62 matched healthy controls.

Results showed that MBP levels in ODEVs from healthy controls were significantly lower than in any of the MS groups. Notably, statistical analysis showed that MBP concentration in ODEVs had a 96.3% accuracy in discriminating patients from controls, suggesting this could be used to improve the diagnosis of MS.

MBP levels also varied across patient groups. PPMS patients had significantly higher levels of this protein in ODEVs than those with RRMS or CIS, with the difference even greater when the two relapsing forms were grouped together, the team noted.

MBP levels could differentiate between patients with distinct disease types

Therefore, MBP levels could effectively differentiate between MS patients with distinct disease types. No significant differences were observed between CIS and RRMS patients.

“Because CIS can, but does not always evolve into RRMS over time, it will be interesting to verify in longitudinal studies whether the MBP concentration in ODEVs will be able to predict which CIS patients will develop RRMS,” the researchers wrote.

In a final set of statistical analyses, the team found that MBP levels correlated with disease severity, measured with either the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score, which adjusts EDSS scores based on disease duration.

The results in this study indicate that “a minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis,” the researchers concluded.

“It will be interesting to design follow-up studies on patients in the initial phases of the disease in order to verify whether MBP concentration in ODEVs will allow the precocious identification of different clinical MS phenotypes,” they added.

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