The objective of this Translational Research Center for CAM therapy of Asthma is to identify antioxidant Complementary and Alternative Medicine therapies for application in asthma. To achieve this objective, we have assembled a team of investigators uniquely qualified for their roles in this project. Project 1 (Phase I Clinical Screening of CAM therapies for asthma, Drs. Peden, PPG PI, Alexis, Bromberg & Patel, UNC) will screen the effect of CAMs initially identified by Drs. Jiang and Ames (gamma tocopherol) or newly identified by Projects 2 & 3 in allergic asthmatic volunteers for Phase I proof of concept studies to determine in CAM therapies protect against endotoxin, O3, and allergen induced airway inflammation. Project 2 of the PPG (Preclinical evaluation of CAM therapies for asthma, Drs. Wagner & Harkema, MSU) will evaluate anti-inflammatory CAMs (or CAMs + traditional therpies) identified by Project 3 in allergen sensitized rodents determining if these CAMs, alone and in combination with traditional asthma therapies, blunt exacerbation of airway inflammation due to allergen, endotoxin and ozone (commonly encountered causes of asthma exacerbation). They will also carry out classic animal pathology and pharmacokinetic studies of CAMs. Project 3 of the PPG (Mechanistic Discovery of CAM Therapies for Asthma, Drs. Jiang, Illek and Ames at CHORI), will employ molecular and cellular techniques to examine the actions of tocopherols, ascorbate, polyphenols (genistein and resveratrol) on generation of oxygen radicals by MPO and EPO, mediator production via cyclo-oxygenase and lipoxygenase, and cellular activation via MAP kinases and NF-kB, and impact on epithelial cell physiology. A Biochemistry Core (Dr. Ames, core leader) will assess samples for products of tocopherol oxidation and oxidative burst and a Biomarker and Sample Repository Core (Dr. Patel, core leader) will provide support for cytokine and mediator assessment of samples and tissues for all projects. These studies will be coordinated via quarterly conference calls and semi-annual meetings of the project and core leaders rotated among the study sites. UNC will maintain a server accessable by all investigators to facilitate data sharing and planning of eventual human volunteer studies. Use of antioxidants is an under-investigated area and it is highly likely that these CAM agents will be effective in prevention of asthma exacerbation mediated by inflammatory processes.
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