Where knowledge is power

Aspiring for a simple, blood-based test to predict MS severity

By Tatiana Plavina, Ph.D.
Associate Director, Value Based Medicine

May 2, 2017

One of the holy grails in multiple sclerosis research is the discovery of a robust molecular marker which can be readily measured in blood to help predict whether a patient’s disease is likely to have a fast-progressing or milder course. Such a biomarker would benefit both doctors and patients by giving them early notice if aggressive steps are needed to help slow disease progression.

Although biomarker discovery in MS is a very active area of research and has been for a number of years, the task is complicated by the remarkable heterogeneity of the disease, its long and often relapsing course, and availability of several treatments that can change biomarker levels. Biogen’s Value Based Medicine group is researching this area, including genetic and epigenetic regulation, gene expression as well as protein and metabolite levels. We recently reported some of our findings at the annual meeting of the American Academy of Neurology in Boston. These results are incredibly exciting to help propel the development of a simple blood test that can inform MS diagnosis and treatment through a blood test.

These findings concern a protein, called neurofilament light (NfL), which has been actively studied in the last couple decades as a marker of neuronal damage. It is now known to be elevated in both cerebrospinal fluid and serum in a variety of neurological conditions, such as MS, amyotrophic lateral sclerosis, Parkinson’s disease, and even traumatic brain injury. Because of the neuronal specificity and its increased levels upon tissue damage, neurofilament light could be compared to the well-known cardiac protein troponin I, that signals heart damage, and used clinically for diagnosis of heart attack.

Many earlier studies of NfL relied on measurements of NfL in cerebrospinal fluid, making it impractical for clicnical practice as CSF collection is a relatively invasive procedure. Recently, with development of a very sensitive assay based on the Single Molecule-Array (SimoaTM) technology, NfL can be measured in blood (serum) of MS patients.

It has been shown that serum NfL levels are associated with clinical and MRI disease activity in MS patients, however, there is no information as to the ability of NfL to predict the long-term disease course which is very important in chronic relapsing disease such as MS.

To research this question, we partnered with researchers at the University Hospital of Basel in Basel, Switzerland, who have developed a serum NfL test. In addition, we harnessed a 25-year-old study conducted by Biogen as part of the phase 3 clinical trial of Avonex, the first biologic drug for MS, that included collection of CSF and serum samples. This legacy study also involved long-term follow-up of MS patients, at 8 and 15 years, and included both clinical and MRI data. In short, it provided the means to robustly test whether or not NfL levels are associated with long-term disease progression.

The results showed that NfL levels in the blood (as well as in cerebrospinal fluid) are tied to more severe MS outcomes in this patient group — that is, the higher the NfL levels in the first couple years of the disease, the more aggressive its course. Moreover, our data suggest that pairing an NfL blood test with other clinical tests, such as MRI scans, might further improve the prognostic power of the test, and help doctors determine whether more intensive MS therapy is needed.

Now, we are working to extend our initial study by validating these results in an independent patient cohort. We are also examining how early NfL can be detected in MS, how stable are the NfL levels, and whether multiple measurements during the course of the disease can increase its prognostic value.

To be sure, it is still early days for serum NfL and its potential use as a clinical biomarker in MS and further research is necessary.

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