TYSABRI PROPOSED MECHANISM OF ACTION

TYSABRI binds to α4-integrin, inhibiting the migration of lymphocytes into the CNS by retaining them in the periphery1

  • TYSABRI is believed to exert its efficacy by binding to the surfaces of lymphocytes and blocking their transmigration across the blood-brain barrier1
  • TYSABRI binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s)1

The specific mechanism(s) by which TYSABRI exerts its effects in relapsing MS have not been fully defined.

In demyelinating diseases such as MS, evidence suggests α4-integrin may play a key role in inhibiting CNS migration of lymphocytes—a trigger in the inflammatory process in MS1,2

TYSABRI is a monoclonal antibody that binds to α4-integrin—a known target in the pathogenesis of MS

  • The α4 subunit α4β1 integrin is expressed on the surface of all leukocytes (except neutrophils)

TYSABRI may exert its effects by blocking the interaction of α4-integrin with adhesion molecules on the vascular endothelium

This may prevent the migration of leukocytes across the blood-brain barrier, inhibiting further recruitment and inflammatory activity of activated immune cells

TYSABRI may further act to inhibit the interaction of α4-expressing leukocytes with their ligands in the extracellular matrix and on parenchymal cells, thereby inhibiting further recruitment and inflammatory activity of activated immune cells

CNS=central nervous system.