Cerebrospinal fluid NCAM levels are modulated by disease modifying therapies

Abstract

Background

Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated thatsoluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the CSF of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease‐modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS.

Methods

We measured CSF sNCAM levels at baseline and after 12‐24 months of DMT in 69 patients, 49 relapsing‐remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in‐house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured.

Results

At baseline, the mean sNCAM level was 268.7 ng/ml (SD 109 ng/ml) in MS patients compared with 340.6 ng/ml (SD 139 ng/ml) in HC, and PMS had significantly lower sNCAM (239.2 ng/ml, SD 123.0, p=0.019) compared to RRMS (269.4 SD 127.4, p=0.043). After natalizumab and mitoxantrone treatment, we observed an increase of mean sNCAM. However, in the fingolimod treated group, mean sNCAM decreased. There was no correlation was found with EDSS or MSSS, or NfL levels as a whole.

Conclusions

CSF sNCAMwere found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Followingnatalizumab and mitoxantrone treatment, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disabilityin the short‐term or NfL levels.

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