UC Davis Physician-Scientist Advancing Treatment of Severe Asthma
To study adult severe asthma, Dr. Zeki began working with Dr. Nicholas Kenyon, who is the current Chief of the Division of Pulmonary, Critical Care, and Sleep Medicine. He was particularly interested in understanding mechanisms of the mevalonate pathway, which is modulated by the cholesterol-inhibiting family of drugs called ‘statins’ or HMG-CoA reductase inhibitors. Starting with observational data in patients with severe asthma who were on oral statins (for the treatment of coronary artery disease or hyperlipidemia), he found that asthmatics on a statin drug had improved symptom control and predicted a lower rate of acute exacerbations.
Dr. Zeki initially tested the idea that statins given systemically might help control the inflammation and airways hyperresponsiveness associated with severe asthma in mouse models of asthma. He then showed that taking a statin via the inhaled route has similar benefits in the asthma mouse model. Based upon his success in small animal models, he initiated the next imperative step, which is to test these compounds in a nonhuman primate prior to initiating a Phase I clinical study in humans.
In his 2014 CNPRC Pilot Program Grant “The Fate of Inhaled Statins in the Lung and Systemic Circulation”, Dr. Zeki will investigate the dosage and airway depositions of inhaled statins, namely pravastatin and simvastatin, with the intent of optimizing dosage delivery prior to testing in human subjects. He sees the pilot program as an excellent opportunity for junior investigators to generate critical pre-clinical data that will lead to successful funding of clinical trials for severe asthma through the National Institutes of Health. Dr. Zeki believes that this study is an essential stepping stone to bring new and innovative therapies to patients with severe asthma.
The CNPRC Pilot Research Program provides a mechanism by which Principal Investigators in any discipline, and particularly those that are not closely related to the Center’s categorical Research Units, may have full opportunity to use the Center’s resources. This program serves as a resource to the entire biomedical research community, including regional, national and international researchers. It is targeted for scientists new to nonhuman primate research and particularly encourages junior investigators to apply.
Dr. Amir Zeki, UC Davis, Division of Pulmonary, Critical Care, and Sleep Medicine, and research assistant Sean Ott discuss results of the effects of simvastatin on Interleukin-13 signaling in human airway epithelial cells.