Wobbing Neurofilament levels in MS what do they mean for PROXIMUS

Gresle MM, Liu Y, Dagley LF, Haartsen J, Pearson F, Purcell AW, Laverick L, Petzold A, Lucas RM, Van der Walt A, Prime H, Morris DR, Taylor BV; on behalf of the Ausimmune Consortium, Shaw G, Butzkueven H. Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients. J Neurol Neurosurg Psychiatry. 2014. doi: 10.1136/jnnp-2013-306789. [Epub ahead of print]. 

OBJECTIVESWe evaluated whether the measurement of serum phosphorylated neurofilament heavy chain (pNF-H) titre is likely to be a valid biomarker of axonal injury in multiple sclerosis (MS).

METHODS: Serum pNF-H concentrations were measured by ELISA in cases with relapsing-remitting (RR)-MS (n=81), secondary progressive (SP) MS (n=13) and primary progressive (PP)-MS; n=6) MS; first demyelinating event (FDE; n=82); and unaffected controls (n=135). A subset of MS cases (n=45) were re-sampled on one or multiple occasions. The Multiple Sclerosis Severity Score (MSSS) and MRI measures were used to evaluate associations between serum pNF-H status, disease severity and cerebral lesion load and activity.

RESULTS: We confirmed the presence of pNF-H peptides in serum by ELISA. We showed that a high serum pNF-H titre was detectable in 9% of RR-MS and FDE cases, and 38.5% of SP-MS cases. Patients with a high serum pNF-H titre had higher average MSSS scores and T2 lesion volumes than patients with a low serum pNF-H titre. Repeated sampling of a subset of MS cases showed that pNF-H levels can fluctuate over time, likely reflecting temporal dynamics of axonal injury in MS.

CONCLUSIONS: A subset of FDE/MS cases was found to have a high serum pNF-H titre, and this was associated with changes in clinical outcome measures. We propose that routine measurement of serum pNF-H should be further investigated for monitoring axonal injury in MS.

The PROXIMUS study has just been given the green light after many, many months since this study has first supported.This delay has been related to the review process and most importantly ensuring that the assay meets the necessary regulatory requirements. In this current study assaying neurofilament heavy (the Heavy means the molecular weight is the largest) there was some variation from time of assay and it was higher when the lesion load was more active. In the PROXIMUS study the original plan was to perform one baseline measurement but on advice this has been increased I believe to two because of the potential for variation, . We should be recruiting very soon

CoI; ProfG is PI on the PROXIMUS study

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