Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri®) in inflammatory diseases

Olaf Stüve, Jeffrey L. Bennett

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)79-95
Number of pages17
JournalCNS Drug Reviews
Volume13
Issue number1
DOIs
StatePublished - Mar 2007

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Toxicology
Pharmacology
Integrin alpha4beta1
Multiple Sclerosis
Progressive Multifocal Leukoencephalopathy
Clinical Trials
Antibodies, Monoclonal, Humanized
Natalizumab
Relapsing-Remitting Multiple Sclerosis
Polyomavirus
Opportunistic Infections
Integrins
Leukocytes
Therapeutics
Central Nervous System
T-Lymphocytes
Safety
Incidence
Brain

Keywords

  • Experimental autoimmune encephalomyelitis
  • Interferon beta
  • Multiple sclerosis
  • Natalizumab
  • Very late activating antigen 4

ASJC Scopus subject areas

  • Pharmacology
  • Neuropsychology and Physiological Psychology

Cite this

Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri®) in inflammatory diseases. / Stüve, Olaf; Bennett, Jeffrey L.

In: CNS Drug Reviews, Vol. 13, No. 1, 03.2007, p. 79-95.

Research output: Contribution to journalArticle

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