An increasing number of available treatment options promote the possibility of individualised management of patients with multiple sclerosis (MS). But how can disease prognosis and treatment success best be evaluated? Molecular biomarkers can be useful in this regard across different phases of MS disease and are broadly divided into five categories.
Due to difficulty in validating molecular biomarkers, only a few are routinely used in clinical practice to date. Therefore, cutting edge research within the field is focused on finding set indicators for disease development, relapse prediction, and response to treatment.
Yuan and Nixon (2021) reviewed neurofilament proteins (NfPs), which are currently considered promising among biomarkers in MS. NfPs are released in response to neuronal damage and their levels in the cerebrospinal fluid have been found to be elevated in patients with MS. In clinical studies the NfPs were useful in evaluating disease activity, brain atrophy, or worsening disability. Recent advances allowing for measuring NfPs from blood samples through ultrasensitive assays further fuels their versatility, allowing for repeated measurements with minimal invasiveness for patients.
However, the recent ASCEND cohort study by Gafson et al. (2022) found that the concentration of serum neurofilament light (sNfL), a type of NfP, did not appear to be a dynamic biomarker associated with current or future disability progression in secondary progressive MS (SPMS). These results are consistent with a similar study in relapsing-remitting MS (RRMS). A constant low sNfL concentration within the cohort may indicate that disease progression may be unrelated to loss of neurons or that the degradation and turnover time of sNfL are too short to be sensitive to a chronic disease course. The study has several limitations and requires further validation but adds insight into the usage of NfPs as MS biomarkers.
Other biomarkers worth keeping an eye on are glial fibrillary acidic protein (GFAP) and contactin-1 (CNTN1).According to a clinical study by Sharquie et al. (2020), increased levels of GFAP in serum were suggested to correlate with exacerbation of disease, hence GFAP being pinpointed as a useful indicator for disease activity. In contrast, van Lierop et al. (2022) recently reported that lower serum concentrations of CNTN1 were associated with long-term disability progression.
CNTN1=contactin-1; GFAP=glial fibrillary acidic protein; MS=multiple sclerosis; NfPs=neurofilament proteins; sNfL=serum neurofilament light; RRMS=relapsing-remitting multiple sclerosis; SPMS=secondary progressive multiple sclerosis.