Abstract
Objective: To assess the relationship between plasma Osteopontin (pOPN) levels and cognitive performances before and during 2 year Natalizumab (NTZ) treatment in Relapsing Multiple Sclerosis (RRMS) patients. Background Increased plasma and cerebrospinal fluid (CSF) OPN levels were reported in patients with MS, Alzheimer disease and HIV-associated dementia. A marked decline of CSF OPN levels during NTZ treatment has been recently described in RRMS patients. Design/Methods: Forty-three RRMS (33 F, mean age 34.3±10.4 years, mean disease duration 9.9±5.3 years, median EDSS [range]3.5[2.0-5.5]) scheduled for NTZ treatment and 22 age- and gender-matched Healthy Controls (HCs) were enrolled. pOPN levels were assessed by a commercial ELISA kit on plasma samples at baseline and every 6 months for 2 years. Cognitive performances were assessed, by the Brief Repeatable Battery, at baseline and every 12 months. A global Cognitive Impairment Index (CII) was calculated for each patient. The correlations between different parameters were evaluated through the Partial correlation test. Results: Baseline pOPN levels were significantly (Mann-Whitney test; p=.02) higher (65.13±22.91 ng/ml) in RRMS patients than in HCs (53.20±12.68). Cognitive impairment (failure≥3 tests) was detected in 27.9% of RRMS. In RRMS patients, baseline pOPN levels significantly correlated (r=.59, p=.004) with CII values (median 14; range 0-27). pOPN levels significantly (p=.036) decreased after 1(n=24; 56.19±17.63) and 2 (n=8; 36.87±8.71) years of NTZ treatment. Median CII significantly (p=.029) decreased during NTZ treatment to 9 (range 0-28) at year 1 and to 3.5 (range 0-18) at year 2. A significant correlation between the reduction of the CII and of the pOPN levels was found (r=.442; p=0.045) at year 1. Conclusions: these results suggest a possible role of OPN as a bridge protein between inflammation and neurodegeneration in RRMS and a beneficial effect of NTZ on cognitive performances partially related to a reduction of pOPN levels. Disclosure: Dr. Iaffaldano has nothing to disclose. Dr. Ruggieri has nothing to disclose. Dr. Viterbo has received personal compensation for activities with Biogen Idec and Novartis. Dr. Mastrapasqua has nothing to disclose. Dr. Paolicelli has received personal compensation for activities with Merck, Serono, Bayer Schering Pharma, and Biogen Idec. Dr. Lucchese has nothing to disclose. Dr. Trojano has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec and Sanofi-Aventis Pharmaceuticals, Inc. as a consultant and/or speaker. Dr. Trojano has received research support from Merck & Co., Inc.
Published Version
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