Research: Measuring Nerve Damage

Epub: Kuhle et al. A comparative study of CSF neurofilament light and heavy chain protein in MS. Mult Scler. 2013 Mar 25. 

BACKGROUNDThere is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)).

METHODS: We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light® enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfHSMI35 assay.

RESULTS: Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls (p ≤ 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease (rs = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfHSMI35 in both CIS patients (p = 0.001) and all MS stages grouped together (p = 0.035).

NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light® ELISA performed better in discriminating patients from controls, compared with the ECL-NfHSMI35 immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.

This study looked for the presence of neurofilaments, which are the scaffolding of nerves, see Annie’s talk on PROXIMUS trial at the Research Day. There are different sizes of this molecule one is called heavy and another light, because it is smaller. To get a handle of what is going on, notably in relation to nerve damage and loss, spinal taps were done and the presence or absence of neurofilaments within the cerebrospinal fluid were examined. This study found that measuring the light version gave more robust results than the heavy version. This is why this light version will be measured in the the PROXIMUS trial.
CoI: Members of Team G did this work

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  • Use of NfL and GFAP for biomarkers of nerve degeneration will be more efficacious than performing MRI. Are these proteins detectable in serum? Drawing blood would obviously be more desirable than performing LP.

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