TY - JOUR
T1 - Anti-α4 integrin therapy for multiple sclerosis
T2 - Mechanisms and rationale
AU - Rice, George P.A.
AU - Hartung, Hans Peter
AU - Calabresi, Peter A.
PY - 2005/4/26
Y1 - 2005/4/26
N2 - The symptoms, severity, and course of multiple sclerosis (MS) vary among patients, leading to complex treatment issues. In recent years, research has focused on specific adhesion molecules that participate in the activation and function of lymphocytes, especially the migration of these cells to sites of inflammation. In particular, the integrin, very late activation antigen (VLA)-4, has been implicated in mediating adhesion and migration of immune cells through interaction with its ligand, vascular cell adhesion molecule (VCAM)-1. VLA-4 is comprised of α4/β1 and is critical in mediating Th-1 cell migration in the animal model of MS, experimental autoimmune encephalomyelitis, and has been the target of several recent clinical trials in MS. The humanized monoclonal antibody to α4 integrin, natalizumab (Tysabri, Biogen Idec/Elan), was recently approved in the United States for the treatment of relapsing MS. The authors discuss the mechanisms by which α4 integrins alter lymphocyte function as a rationale for anti-α4 integrin use in MS.
AB - The symptoms, severity, and course of multiple sclerosis (MS) vary among patients, leading to complex treatment issues. In recent years, research has focused on specific adhesion molecules that participate in the activation and function of lymphocytes, especially the migration of these cells to sites of inflammation. In particular, the integrin, very late activation antigen (VLA)-4, has been implicated in mediating adhesion and migration of immune cells through interaction with its ligand, vascular cell adhesion molecule (VCAM)-1. VLA-4 is comprised of α4/β1 and is critical in mediating Th-1 cell migration in the animal model of MS, experimental autoimmune encephalomyelitis, and has been the target of several recent clinical trials in MS. The humanized monoclonal antibody to α4 integrin, natalizumab (Tysabri, Biogen Idec/Elan), was recently approved in the United States for the treatment of relapsing MS. The authors discuss the mechanisms by which α4 integrins alter lymphocyte function as a rationale for anti-α4 integrin use in MS.
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U2 - 10.1212/01.WNL.0000158329.30470.D0
DO - 10.1212/01.WNL.0000158329.30470.D0
M3 - Review article
C2 - 15851719
AN - SCOPUS:17644398787
SN - 0028-3878
VL - 64
SP - 1336
EP - 1342
JO - Neurology
JF - Neurology
IS - 8
ER -