Inflammation Research
The Inflammation division of Wyeth Discovery Research is committed to the discovery of novel agents to control inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and multiple sclerosis (MS). The department is organized into three interactive subgroups: Molecular Inflammation, Immunology / RA and MS and Respiratory Diseases.
Immunology / RA and MS
Chronic inflammatory responses contribute to the initiation and persistence of Rheumatoid Arthritis (RA) and other autoimmune diseases. The Immunology / RA / MS group focuses its research efforts on the development of new, immune-based therapies for the treatment of RA, Systemic Lupus Erythematosus (SLE), Psoriasis, Inflammatory Bowel Disease, and Multiple Sclerosis. Research projects in the group focus on both innate and adaptive immune responses, with an emphasis on modulation of B and T cell responses. Leading scientists within the group have pioneered work in new cytokine discovery, leading to exciting new therapeutic targets for chronic inflammatory disease, including IL-21 receptor and IL-22 receptor activation. The group has significant expertise in T cell activation pathways, leading to therapeutic strategies targeting costimulatory pathways and intracellular signaling pathways. Through an exciting new alliance with Trubion Pharmaceuticals, the group is developing new protein therapeutics directed at pathogenic B cell populations in inflammatory disease. Small molecule drugs targeting B cell activation are also under development. Additional research projects are based upon modulation of innate immune responses and include modulation of Toll-like receptor signaling, and exploration of regulatory T cells. Collaborations with leading academic scientists strengthen our research base and help sustain our leadership in discovery and development of new therapeutic approaches for the treatment of chronic inflammatory diseases.
Molecular Inflammation
Biologics blocking tumor necrosis factor alpha (TNF) have had a dramatic impact on the treatment of multiple autoimmune diseases. The Molecular Inflammation group is using its extensive expertise in the biology of TNF production to develop small molecules that will inhibit the production of TNF in inflammatory diseases. Blockade of immune cell migration and trafficking is another promising therapeutic intervention pursued by Molecular Inflammation. Sites of inflammation are characterized by the presence of immune cell infiltrates that induce, enhance and perpetuate disease by generating mediators such as cytokines, eicosanoids and proteolytic enzymes. A major mechanism of inflammatory cell migration is based on the formation of gradients of peptidic and lipid chemoattractants that act on G-protein Coupled Receptors or GPCRs. Activation of GPCRs on white blood cells direct their movement from the bloodstream to inflammatory sites. The Molecular Inflammation group has established immune cell anti-migration programs by interfering with the interaction of several chemoattractant / GPCR pairs. They have developed a state-of-the-art assay platform that includes measurements of early biochemical signaling cascades that result from receptor activation as well as in vitro migration assays that model this important biological phenomenon.
Respiratory Diseases
It is clear that inflammation plays a key role in the pathology of asthma and chronic obstructive pulmonary disease (COPD). Although the incidence of asthma and COPD continues to increase dramatically worldwide, causing significant morbidity and mortality, few new drugs have emerged to treat the more severe forms of these serious and potentially life threatening diseases. The goal of the respiratory disease research group at Wyeth is to deliver new and innovative therapies to treat asthma, COPD and other respiratory disorders. To accomplish this goal we have assembled a world-class Group of scientists engaging in cutting-edge research dedicated to advancing our understanding of the biology of asthma and COPD. Current projects are aimed at targeting interleukin-13 (IL-13), a pivotal regulatory cytokine in asthma, and antagonizing cytosolic phospholipase A2 (cPLA2), a potent inflammatory mediator. In addition, we have established strategic collaborations with academic and industrial research leaders to expand our knowledge and enhance our ability to discover innovative new drugs. At Wyeth, we believe that this focused effort to understand the biology of asthma and COPD will lead to the identification of important disease mechanisms, identification of exciting new drug targets, and development of novel therapeutics to improve the quality of life for those suffering from asthma and COPD.