Blood biomarker to pick up progression. Time for more effective treatment?


Neurofilaments are internal nerve proteins and if you are picking them up in the blood it is a sign of nerve damage. Neurofilament light (the smallest of the three types-light, medium and heavy) elevates during neuroinflammatory disease and responds to treatment in relapsing MS. This study says that there is nerve damage in progressive MS in people who are worsening.

We know progressive MS is associated with nerve damage. However, what is causing it the neuroinflammation that triggers attacks and relapses or the neuroinflammation that is associated with the slow damage. Many people would think they are looking at the effect of the latter, but if it is the former, we have the tools to something about it.

This perhaps says that these people should be taking effective disease modifying treatment and neuroprotection.

If we looked in the EAE mice we could pick blood neurofilaments up during the time active lesios were present, but in the progressive phase where we had effectively controlled relapsing neurofilamatory disease then we could not detect the neurofilaments in the blood. At the time we did this we would have struggled to get enough CSF from a mouse to do the assay. But with the simoa it would be possible. However, this work implicates neurofilaments as a sensitive marker of “active” neuroflammation. This could be god news as it could mean an alternative to gadolinium-enhancing magnetic resonance imaging. Based on post-morem tissue we know that this “active” inflammation is present in most people with MS. We also know that some immunosuppressive drugs may not be good enough to stop this inflammation in the brain. Neuroprotective agents like ibudilast are not good enough to stop the active lesions forming based on previous trials. This is why we need to think of combination treatment. Did it stop neurofilament levels in the blood or the CSF?

Plasma Neurofilaments correlate with Disability in Progressive Multiple Sclerosis patients. Ferraro D, Guicciardi C, De Biasi S, Pinti M, Bedin R, Camera V, Vitetta F, Nasi M, Meletti S, Sola P. Acta Neurol Scand. 2019 Jul 27. doi: 10.1111/ane.13152. [Epub ahead of print]

OBJECTIVES: Cerebrospinal fluid (CSF) and blood neurofilaments (NFL) are markers of axonal damage and are being investigated, mostly in Relapsing-Remitting (RR) MS, as a marker of disease activity and of response to treatment, while there is less data in progressive MS patients. Primary aim was to measure NFL in plasma samples of untreated patients with primary (PP) and secondary (SP) progressive MS and to correlate them with disability, disease severity and prior/subsequent disability progression.

MATERIALS AND METHODS: NFL concentrations were measured using SIMOA (Single Molecule Array, Simoa HD-1 analyzer; Quanterix, Lexington).

RESULTS: NFL concentrations were measured on plasma samples of 70 progressive (27 PP and 43 SP), 21 RRMS patients and 10 HCs. Longitudinal plasma NFL (pNFL) concentrations (median interval between sampling: 25 months) were available for nine PP/SP patients. PNFL concentrations were significantly higher in PP/SP compared to RRMS patients. They correlated with EDSS and MS Severity Score values. There was no difference in pNFL levels between PP/SP patients with EDSS progression in the preceding year (14% of patients) or during a median follow-up of 27 months (41%). In the longitudinal sub-study, pNFL levels increased in all patients between sampling by a mean value of 23% while EDSS mostly remained stable (77% of cases).

CONCLUSION: In PP/SP progressive MS patients, pNFL levels correlate with disability and increase over time, but are not associated with prior/subsequent disability progression, as measured by EDSS, which may not be a sufficiently sensitive tool in this context.

The level of correlation is simply not good enough to be predictive for the individual

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