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. 2007 Apr 24;13(1):79–95. doi: 10.1111/j.1527-3458.2007.00003.x

Pharmacological Properties, Toxicology and Scientific Rationale for the use of Natalizumab (Tysabri®) in Inflammatory Diseases

Olaf Stüve 1,2,3, Jeffrey L Bennett 4,5
PMCID: PMC6494150  PMID: 17461891

ABSTRACT

Natalizumab (Tysabri®) was the first adhesion molecule antagonist to make it into clinical trial for patients with multiple sclerosis (MS) and other inflammatory disorders. Natalizumab is a humanized recombinant monoclonal antibody (MAb) that binds to the alpha (α)4 chain of the α4 beta (β)1 (very late activating antigen 4; VLA‐4) and α4β7 integrins. The scientific rationale for natalizumab therapy is the reduction of leukocyte extravasation into peripheral tissues. Natalizumab, like other VLA‐4 antagonists, may also interfere with the activation of T lymphocytes in secondary lymphoid organs and their reactivation in the central nervous system (CNS).

Shortly after its approval for the treatment of relapsing‐remitting MS (RR‐MS), three patients who were treated with natalizumab in the setting of clinical trials developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyoma virus JC. It remains to be elucidated why the use of this VLA‐4 antagonist is associated with an increased incidence of PML. Natalizumab was recently reapproved for the treatment of relapsing forms of MS. In this review, we outline the scientific rationale for using natalizumab in MS and other inflammatory disorders. In addition, an overview of pharmacological properties, clinical efficacy, safety, and toxicology of natalizumab is provided.

Keywords: Experimental autoimmune encephalomyelitis, Interferon beta, Multiple sclerosis, Natalizumab, Very late activating antigen 4

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Acknowledgments

Acknowledgments This study was supported by a Start‐up Grant from the Dallas VA Research Corporation, a New Investigator Award from VISN 17, Veterans Administration, Research Grants from National Multiple Sclerosis Society (NMSS; RG3427A8/T, and RG2969B7/T), a grant from the Viragh Foundation (O.S.). J.L.B. is supported by Public Health Grants (NS32623 & EY0114573) and a grant from the National Multiple Sclerosis Society (RG3908).

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