Natalizumab (Tysabri®) is the first approved for therapy, commertially available selective antagonist of integrins. Integrins are glycoproteins belonging to adhesion molecules family, which play an important role in the process of cell adhesion. Natalizumab binds to α4 chain of integrins α4β1 and α4β7 present on the surface of almost all subpopulations of leukocytes. Blockade of interaction between integrin and its ligand prevents leukocyte transmigration through endothelium to the tissue site of inflammation. The clinical efficacy of natalizumab in remitting-relapsing MS was analyzed in two multicenter, randomized and placebo controlled third phase clinical trials: AFFIRM (Natalizumab Safety and Efficacy in RR-MS) and SENTINEL [Safety and Efficacy of Natalizumab in Combination with Avonex (IFN-β-1α) in Patients with MS). In AFFIRM trial natalizumab was evaluated in monotherapy, in SENTINEL study as add on therapy to IFN-β-1α. Both trials confirmed that natalizumab is beneficial in all analyzed endpoints. There was statistically significant decrease of relapse number and the risk of the disease progression. There was also beneficial influence of natalizumab therapy on the central nervous system (CNS) MRI parameters. After two years of therapy the number of gadolinium-enhanced MS plaques, as well as the number of the new and enlarging hyperintensive T2 plaques, was decreased. Because of the rare but serious side effect (progressive multifocal leukoencephalopathy, PML) the registration of natalizumab was suspended in June 2004. Detailed analysis of the results of both third phase clinical trials led to reapproval of natalizumab to therapy in June 2006. The strict criteria of patients’ inclusion to natalizumab therapy were established to minimize the risk of the serious side effects. 

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Natalizumab: a new way of multiple sclerosis therapy

Marcin Jałosiński, Izabela Jatczak, Andrzej Głąbiński

Affiliation and address for correspondence
Aktualn Neurol 2007, 7 (3), p. 195-201
Abstract

Natalizumab (Tysabri®) is the first approved for therapy, commertially available selective antagonist of integrins. Integrins are glycoproteins belonging to adhesion molecules family, which play an important role in the process of cell adhesion. Natalizumab binds to α4 chain of integrins α4β1 and α4β7 present on the surface of almost all subpopulations of leukocytes. Blockade of interaction between integrin and its ligand prevents leukocyte transmigration through endothelium to the tissue site of inflammation. The clinical efficacy of natalizumab in remitting-relapsing MS was analyzed in two multicenter, randomized and placebo controlled third phase clinical trials: AFFIRM (Natalizumab Safety and Efficacy in RR-MS) and SENTINEL [Safety and Efficacy of Natalizumab in Combination with Avonex (IFN-β-1α) in Patients with MS). In AFFIRM trial natalizumab was evaluated in monotherapy, in SENTINEL study as add on therapy to IFN-β-1α. Both trials confirmed that natalizumab is beneficial in all analyzed endpoints. There was statistically significant decrease of relapse number and the risk of the disease progression. There was also beneficial influence of natalizumab therapy on the central nervous system (CNS) MRI parameters. After two years of therapy the number of gadolinium-enhanced MS plaques, as well as the number of the new and enlarging hyperintensive T2 plaques, was decreased. Because of the rare but serious side effect (progressive multifocal leukoencephalopathy, PML) the registration of natalizumab was suspended in June 2004. Detailed analysis of the results of both third phase clinical trials led to reapproval of natalizumab to therapy in June 2006. The strict criteria of patients’ inclusion to natalizumab therapy were established to minimize the risk of the serious side effects. 

Keywords
natalizumab, multiple sclerosis, immunomodulation treatment, adhesive molecules, integrines

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