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Title: Clinical Trials Show Potential of Immunomodulators for Asthma Treatment: Presented at AAAAI

"Clinical Trials Show Potential of Immunomodulators for Asthma Treatment: Presented at AAAAI"

By Maggie Schwarz PHILADELPHIA -- March 24, 2008 -- Asthma patients will benefit from the development of a number of new agents that specifically inhibit key immunopathogenic mechanisms, according to researchers speaking here at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. Thomas B. Casale, MD, Professor of Medicine and Medical Microbiology and Immunology; and Jeffrey R. Stokes, MD, Associate Professor of Medicine, and Division Chief, Allergy and Immunology Division, both at Creighton University, Omaha, Nebraska, reviewed upcoming immunomodulators in clinical trials for allergic respiratory disorders. "Novel therapeutic approaches under study include toll-like receptor (TLR) agonists, oral and parenterally administered cytokine blockers, specific cytokine receptor antagonists, and transcription factor modulators," stated Dr. Casale in a presentation on March 18. Among the TLR4 agonists, CRX-675 has improved nasal symptoms, and clinical studies are identifying dosing and timing parameters for this agent. Among TLR9 agonists, or immunostimulatory oligonucleotides, these agents hold promise for allergic disorders in addition to potential as adjuvants in cancer therapies and vaccines against hepatitis B and C, anthrax, and influenza. The interleukin (IL)-5 antibody mepolizumab is showing promise in eosinophilic esophagitis, and at least three IL-13 humanized monoclonal antibodies are under development. An investigational inhaled IL-4Rmu receptor antagonist reduced the late-phase asthmatic response by 72% in a phase 2a trial. It also reduced levels of exhaled nitric oxide and improved pulmonary function in this cohort of asthmatic patients. Antagonists of the tumor necrosis factor family ligands and receptors BAFF and APRIL are in clinical trials for a number of autoimmune disorders and could offer therapeutic benefit in respiratory diseases. Among the Syk kinase inhibitors, R-343 is in development for intrapulmonary delivery for allergic asthma. In the category of peroxisome proliferator-activated receptor-g agonists, several small trials are underway in allergic respiratory disease. Dr. Casale stressed that the goal of immunomodulators is to induce immune tolerance, changing the immune response so that treatment discontinuation can result in long-lasting therapeutic benefits. He is optimistic that new agents under development will inhibit specific immunopathogenic mechanisms to the ultimate benefit of patients with allergic respiratory disease. Studies were funded by Genentech, Inc. and Novartis Pharmaceuticals Corporation. [[Presentation title: Immunomodulators for Allergic Respiratory Disorders.]

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