A marker to monitor treatment response

Amor S, van der Star BJ, Bosca I, Raffel J, Gnanapavan S, Watchorn J, Kuhle J, Giovannoni G, Baker D, Malaspina A, Puentes F. Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis. Mult Scler. 2014 Feb 10. [Epub ahead of print]

BACKGROUND: Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS).

OBJECTIVE: To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS.
METHODS: The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels.
RESULTS: NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (p<0.001). NF-L antibody levels were lower in natalizumab treated than in untreated patients (p<0.001). In the longitudinal series, NF-L antibody levels decreased over time and a significant difference was found following 24 months of treatment compared with baseline measurements (p=0.001).
CONCLUSIONS: Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS.
We have been reporting on the use of measuring neurofilament Light in studies such as PROXIMUS as marker of nerve damage, but with proteins such as these floating about in the blood there is a chance of this generating an antibody response. This study  by DoctorLove demonstrates just that and shows that a neurofilament reactive response generates in MSers and that this decreases over time following treatment of tysabri. We know that this treatment blocks lesion formation and this is associated with reduced neurofilament in the spinal fluid. Therefore as neurofilament is lost from the spinal fluid it will also disappear from the blood and so the factor that drives neurofilament antibody will be lost and so it will go from the blood also. It can therefore be used as a marker to monitor therapeutic activity.

However, what else does this mean (a) it may block the capacity to detect neurofilaments in blood if the antibody blocks the site used in the detection of neurofilament making the neurofilament response look less. However, it can make the neurofilaments hang around in blood for longer and so make it easier to detect but importantly it can make MS worse and could contribute to nerve damage but that’s another story.

CoI: Work from Team G

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