Natalizumab

Summary

Natalizumab is a recombinant humanized IgG4k monoclonal antibody with an approximate molecular weight of 149kD.  It's biological target is the α4 subunits α4-β1 and α4-β7 integrins (VCAM-1 and MAdCAM-1, respectively).  Binding of natalizumab to it's target prevents transmigration of leukocytes across endothelial surfaces to sites of inflammation.  Natalizumab is indicated for the treatment of both Crohn's disease (CD) and relapsing forms of multiple sclerosis (MS). 

The FDA has issued a black box warning regarding the risk of progressive multifocal leukoencephalopathy (PML) in patients receiving natalizumab.  Concerns about natalizumab causing PML surfaced when two patients with MS and one with CD developed JC polyomavirus associated PML while being treated with this monoclonal antibody.  Until further notice, natalizumab is available only through a restricted distribution program, and all pateints being treated with natalizumab must be followed carefully for the development of PML.

Brand Name

Tysabri

Other Names

Molecular Target

α4-subunit of α4-β1 and α4-β7 integrins; blocks binding of VLA4 to VCAM-1 and binding of α4-β7 to MADCAM-1

Molecular Structure

Humanized IgG4κ monoclonal antibody, recombinant

Licensed Indication, Major Target Diseases

Crohn's Disease; Relapsing Forms of Multiple Sclerosis

Manufacturer/Distributor

Elan Pharmaceuticals & Biogen Idec

References