Natalizumab: targeting alpha4-integrins in multiple sclerosis

Engelhardt, Britta; Kappos, Ludwig (2008). Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegenerative diseases, 5(1), pp. 16-22. Basel: Karger 10.1159/000109933

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In 1992, it was shown that monoclonal antibodies blocking alpha(4)-integrins prevent the development of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS). As alpha(4)beta(1)-integrin was demonstrated to mediate the attachment of immune-competent cells to inflamed brain endothelium in experimental autoimmune encephalomyelitis, the therapeutic effect was attributed to the inhibition of immune cell extravasation and inflammation in the central nervous system. This novel therapeutic approach was rapidly and successfully translated into the clinic. The humanized anti-alpha(4)-integrin antibody natalizumab demonstrated an unequivocal therapeutic effect in preventing relapses and slowing down the pace of neurological deterioration in patients with relapsing-remitting MS in phase II and phase III clinical trials. The occurrence of 3 cases of progressive multifocal leukoencephalopathy in patients treated with natalizumab led to the voluntary withdrawal of the drug from the market. After a thorough safety evaluation of all patients receiving this drug in past and ongoing studies for MS and Crohn's disease, natalizumab again obtained approval in the US and the European Community. A treatment targeting leukocyte trafficking in MS has now re-entered the clinic. Further thorough evaluation is necessary for a better understanding of the risk-benefit balance of this new treatment option for relapsing MS. In this review, we discuss the basic mechanism of action, key clinical results of clinical trials and the emerging indication of natalizumab in MS.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Engelhardt, Britta

ISSN:

1660-2854

ISBN:

18075270

Publisher:

Karger

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:05

Last Modified:

17 Mar 2015 22:19

Publisher DOI:

10.1159/000109933

PubMed ID:

18075270

Web of Science ID:

000251736000003

URI:

https://boris.unibe.ch/id/eprint/28200 (FactScience: 118504)

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