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Natalizumab reduces serum pro-angiogenic activity in MS patients

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Abstract

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0 ± 3.9 and 22.5 ± 2.6, p < 0.0001) and higher osteopontin levels (65.7 ± 24.3 ng/ml and 65.9 ± 16.6 ng/ml, p = 0.019 and p = 0.029, respectively) than HCs (9.0 ± 2.2; 48.5 ± 7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs = 0.373, p = 0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9 ± 2.1, p < 0.005; 49.3 ± 20.0 ng/ml, p = 0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.

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Author notes

  1. Domenico Ribatti and Maria Trojano contributed equally to this work.

Authors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Piazza G. Cesare 11, 70124, Bari, Italy

    Pietro Iaffaldano, Domenico Ribatti & Maria Trojano

  2. National Cancer Institute “Giovanni Paolo II”, Bari, Italy

    Domenico Ribatti

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  1. Pietro Iaffaldano
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Correspondence to Maria Trojano.

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Conflict of interest statement

PI has served on scientific advisory boards for Biogen Idec, and has received funding for travel and/or speaker honoraria from Sanofi-Aventis, Biogen Idec, Teva and Novartis. MT has received honoraria for consultancy or speaking from Biogen, Sanofi-Aventis, Merck Serono, and Bayer-Schering and research grants from Merck Serono, Biogen and Novartis. DR declares no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the University of Bari Medical School.

Informed consent

Written informed consent was obtained by all patients before the start of natalizumab (NTZ).

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Iaffaldano, P., Ribatti, D. & Trojano, M. Natalizumab reduces serum pro-angiogenic activity in MS patients. Neurol Sci 39, 725–731 (2018). https://doi.org/10.1007/s10072-018-3266-9

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  • DOI: https://doi.org/10.1007/s10072-018-3266-9

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