Monday, 9 September 2013

Natalizumab can affect cognitive defects...maybe because it stops production of an inflammatory protein

Iaffaldano P, Ruggieri M, Viterbo RG, Mastrapasqua M, Trojano M.The improvement of cognitive functions is associated with a decrease of plasma Osteopontin levels in Natalizumab treated Relapsing Multiple Sclerosis.Brain Behav Immun. 2013 Aug 29. doi:pii: S0889-1591(13)00420-0. 10.1016/j.bbi.2013.08.009. [Epub ahead of print]


Objective To investigate the effect of two-years Natalizumab treatment on plasma Osteopontin levels, cognitive performances and fatigue in RelapsingMultiple Sclerosis (RRMS) patients. Methods Forty-nine RRMS patients scheduled for Natalizumab treatment as second-line therapy were enrolled. Plasma samples of twenty-four treatment-naïve RRMS and 22 Healthy Controls (HCs) were used as controls of baseline Osteopontin levels. Plasma Osteopontin levels, using an enzyme-linked immunosorbent assay, cognitive functions using the Brief Repeatable Battery, and fatigue, by the Fatigue Severity Scale(FSS), were assessed at baseline and every 12 months. A global Cognitive Impairment Index (CII) was calculated for each patient. 

Results Patients scheduled for Natalizumab treatment had higher baseline Osteopontin levels (mean[SD] 65.42[22.20]ng/ml) (p=0.013) than HCs (53.20[12.68]ng/ml), but not different from those in the treatment-naïve RRMS group (67.70[24.23]ng/ml); 30.6% of patients showed a cognitive impairment  and 47.6% complained fatigue interfering with daily activities. 

A significant decrease of mean Osteopontin levels(p<0.005), of mean CII values(p<0.005) and of mean FSS score(p< 0.05) was found during the treatment. Baseline Osteopontin levels significantly correlated (p=0.002) with baseline CII values, and the reduction of the CII values during Natalizumab treatment significantly correlated with the decrease of the Osteopontin levels (p<0.05). No correlations were found between Osteopontin levels and FSS score before and during Natalizumab treatment. Conclusions Natalizumab treatment reduces plasma Osteopontin levels and improves cognition and fatigue in RRMS patients. The results suggest that the improvement of cognitive functions is associated to a decrease of plasma Osteopontin levels.
Nataluzimab inhibits the development of lesions in MS and quells inflammatory activity, which is going to limit the cognitive problems that are impart brought about by inflammatory activity. Osteoponitin is a molecule that affects bone but also a immune modulator and can bind to the receptor target of tysabri. Could it be a biomarker of immune activity. The question is it a chicken and egg and causal or are they two interdependent effects but non-causal effects that osteoponitn has nothing to do with the effect on cognitive behaviour. The plus point is that tysabri improvement on fatigue and cognitive problem scores.

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