New Directions in MS Research
Researchers and clinicians continue to look for ways to speed the diagnosis of MS in patients with suspicious symptoms, monitor the course of the disease, and assess response to treatment. Biomarkers play a major role in those efforts. While findings on MRI studies are the biomarkers most frequently employed and best known to patients, recent research has examined how substances in the blood and cerebrospinal fluid (CSF) may also yield important information. To follow are two studies that examine such findings.
Neurofilament light chain (NfL) is a protein that serves as a biomarker of damage to axons, the parts of a nerve cell that carry messages from the brain to other parts of the body. Recent research has shown that blood levels of NfL are elevated in people with MS. Based on this finding, researchers are investigating additional ways in which NfL levels may reveal evidence of disease course and severity, response to treatment, and other aspects of MS.
One team of investigators recently decided to explore whether serum (blood) levels of NfL are elevated well before a person experiences symptoms of MS. They noted that unrecognized demyelinating events, in which the myelin sheath that covers and protects nerve is damaged, can occur prior to the clinical onset of MS. They added, “Identification of these events at the time of occurrence would have implications for early diagnosis and treatment, as well as the search of causal factors for the disease.”
To see if serum NfL could aid in identifying those events, the researchers conducted a case-controlled study involving active-duty United States military personnel who had serum samples stored in the Department of Defense Serum Repository. They selected 60 people with MS, each of whom either had two serum samples collected before MS onset or with one sample collected before and one after onset of MS. They then matched each of those people with a “control” – a person of the same age, sex, race, ethnicity, and dates of sample collection.
Their analysis found that people who went on to develop MS symptoms had higher serum NfL than their matched controls a median of six years before the clinical onset of the disease. Further, the differences in NfL levels became greater as time to symptom onset became shorter. Meanwhile, for people with MS, the arrival of MS symptoms was marked by a significant increase in serum NfL levels.
The researchers said their findings show that MS has a “prodromal” phase, meaning a build-up to obvious symptoms, which lasts several years. They also noted that the elevated blood NfL levels identified during this period indicate that damage to the nervous system is occurring long before symptoms are apparent.86
While NfL is a topic of intense interest to MS researchers, other potential biomarkers are also being evaluated. For example, a group of Canadian investigators recently reported that plasma levels of a protein known as interleukin-1 receptor antagonist (IL-1RA) can help identify the transition from relapsing-remitting MS (RRMS) to secondary-progressive MS (SPMS).
The researchers analyzed plasma levels of the protein in 110 people with RRMS, 17 people with SPMS, and another 17 people who – based on neurological assessment and Expanded Disability Status Scale (EDSS) scores – were transitioning from RRMS to SPMS. They found that the average level of IL-1RA was markedly higher in patients transitioning to secondary-progressive MS. The mean level was 857.4 pg/ml in the transitioning group, as compared to 299.8 pg/ml in the RRMS group and 156.2 ng/ml in people with SPMS.
Further, plasma levels of IL-1RA were correlated with EDSS scores in people with RRMS and those transitioning to SPMS. Plasma levels of the protein did not, however, correlate with patient age, disease duration, or use of disease-modifying therapy (DMT). A lack of correlation with those patient characteristics actually may enhance the utility of using IL-1RA to identify or confirm transition to SPMS by eliminating “background noise,” or confounding factors that would need to be taken into consideration.
While further research into the protein’s potential role in monitoring disease course is needed, the investigators noted that, “Our results demonstrate that IL-1RA is a novel exploratory biomarker that both correlates with EDSS and may suggest when a patient is either in a transitional clinical phase or has fully converted to SPMS.” 87