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Investigation of latent viruses in patients with multiple sclerosis under treatment with Natalizumab

Abstract

Multiple sclerosis is an inflammatory disease of brain and spinal cord occurring demyelization and axonal degeneration. It is clinically characterized by relapses and remissions of neurological dysfunction. Current treatments for MS are only moderately effective, offering decrease of about 20-30% of relapses for MS patients in early stages. The drug Natalizumab is the latest treatment for MS, being able to reduce relapses by 68%, and also reduce disease progression by 42%. However, the main obstacle to the widespread use of this product is its ability to reactivate latent virus in the CNS. The reactivation of the polyomavirus JC, for example, resulted in PML in several patients under treatment, leading some to death. Compounding the problem, the mechanisms involved in the reactivation of polyoma BKV and JCV by Natalizumab is insufficient, as well as the risk that other viruses are reactivated during treatment. Moreover, there is still no consensus about the average time between the start of treatment and reactivation of these viruses. This project will undertake a detailed monitoring of the possible reactivation of the polyomavirus, herpesvirus and also of the endogenous retroviruses from different families in those patients under treatment with Natalizumab. Still, the action of Natalizumab on the replication of JCV in cells will also be investigated. The results of this study will contribute to a better understanding of the effects of Natalizumab on the reactivation of latent viruses, and should assist in establishing a more secure protocol of treatment in patients carrying these viruses. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NALI, LUIZ HENRIQUE; FINK, MARIA CRISTINA; DO OLIVAL, GUILHERME S.; MORAES, LENIRA; CALLEGARO, DAGOBERTO; TILBERY, CHARLES PETER; VIDAL, JOSE ERNESTO; SUMITA, LAURA MASAMI; PENALVA DE OLIVEIRA, AUGUSTO C.; ROMANO, CAMILA M. Polyomavirus Detection in Multiple Sclerosis Patients Under Natalizumab Therapy: Profile and Frequency of Urinary Shedding. Journal of Medical Virology, v. 89, n. 3, p. 528-534, MAR 2017. Web of Science Citations: 0.
DA SILVA NALI, LUIZ HENRIQUE; MORAES, LENIRA; DOMINGUES FINK, MARIA CRISTINA; CALLEGARO, DAGOBERTO; ROMANO, CAMILA MALTA; PENALVA DE OLIVEIRA, AUGUSTO CESAR. Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients. Arquivos de Neuro-Psiquiatria, v. 72, n. 12, p. 960-965, DEC 2014. Web of Science Citations: 7.
DO OLIVAL, GUILHERME S.; FARIA, THIAGO S.; NALI, LUIZ H. S.; DE OLIVEIRA, AUGUSTO C. P.; CASSEB, JORGE; VIDAL, JOSE E.; CAVENAGHI, VITOR B.; TILBERY, CHARLES P.; MORAES, LENIRA; FINK, MARIA C. S.; SUMITA, LAURA M.; PERRON, HERVE; ROMANO, CAMILA M. Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen. FRONTIERS IN MICROBIOLOGY, v. 4, JUN 26 2013. Web of Science Citations: 15.

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