Finding a biomarker in multiple sclerosis (MS) that translates into clinical meaningfulness has been a real challenge for the biomarkers space in the central nervous system (CNS).
MS is currently diagnosed through magnetic resonance imaging (MRI), which detects brain abnormalities, and lumbar punctures, which test the patient’s cerebrospinal fluid (CSF) for the presence of Oligoclonal Bands (OCBs). However, these procedures are invasive and expensive.
Approximately 85% of patients’ MRIs are very specific for the diagnosis of MS, due to the central vein sign and Dawson’s fingers. Only about 15% of patients with MS do not show those characteristics. In those patients, it can be a challenge to make a diagnosis of MS versus the mimics of the disease. However, MRI assessments are very expensive, require complex analyses after the test, and are difficult to standardise.
Diagnosing MS with biomarkers
These challenges have created opportunities for biomarkers that can be measured by simple blood or urine tests at the point of care. In an article published in the journal Neurology entitled “Blood neurofilament light chain as a biomarker of MS disease activity and treatment response,” researchers found that blood neurofilament light (NfL) chain levels are related to clinical and MRI measures in patients with relapsing-remitting MS (RRMS), which is characterised by acute disease activity, and tends to have more brain lesions and worsening of disability.
NfL is one of the three major components of axonal neurofilaments and a marker of axon degeneration. It is measured with serum and CSF tests and has potential to be a predictive marker for disease activity and disability in MS. NfL is one of the most promising biomarkers for MS as it has the potential to monitor ongoing neurodegeneration and axonal injury. The Nfl samples can be measured by an immunoassay called SIMOA, which is highly sensitive, reliable, and preferred by physicians as it allows for blood or CSF samples to be obtained in an easy and safe way.
One of the most useful aspects of neurofilament biomarkers is their potential use both as a prognostic biomarker in clinical trials for progressive MS and also as a way to correlate with treatment response to Biogen/Elan’s Tysabri (natalizumab), Novartis’ Gilenya (fingolimod), and rituximab. To assess the prognostic value of NfL in MS, researchers collaborated with Novartis and other universities in two Phase III controlled clinical trials testing Gilenya.
Blood samples were assessed for NfL levels in 269 RRMS patients in the FREEDOMS trial, in 320 patients from the TRANSFORMS trial, and in 35 healthy controls to compare with clinical and MRI-related outcomes. The results showed that NfL levels are higher in patients with RRMS, and that Gilenya administration was associated with lower NfL blood levels compared to placebo, suggesting that blood NfL levels are useful in assessing MS treatment response.
An unmet need for non-invasive tests
In MS, there are currently 13 FDA-approved disease-modifying therapies, and having biomarkers to help physicians make decisions about which therapies to use in different patient populations is a key area. There is a great unmet need for simple, inexpensive, and non-invasive tests that could be used to screen for MS.
There is also a need for sensitive assays to use in a clinical setting and biomarkers that monitor ongoing disease activity. Currently, no biomarker has been approved for MS, and one of the biggest challenges of using biomarkers in MS is introducing new tests into this already expensive space.