Predictive and Personalized Medicine for Heart Failure and Asthma Using Genomics
Principal Investigator: Stephen Liggett, MD
Approximately 20 million people in the United States have asthma and another five million people suffer from heart failure. Steven B. Liggett, MD, of the University of Cincinnati College of Medicine, and colleagues are conducting studies that focus on a common mechanism of cell signaling that affects multiple diseases including asthma and heart failure.
Dr. Liggett has studied beta-2 adrenergic receptors in cells and in human clinical trials. Three patents have been issued and three clinical trials published that focus on whether knowing the genetic makeup of beta-2 adrenergic receptors of an individual can predict a patient's response to asthma drugs. The studies represent the first pharmacogenetic marker that can be used to personalize asthma treatment. Additional confirmation clinical trials are currently being conducted.
One of the most promising treatments for heart failure is beta-blockers, acting at the beta-1 adrenergic receptor. However, there is extreme variability in terms of how patients respond to the treatment. (Life expectancy can range from less than one year to more than 10 years.)
Dr. Liggett and his colleagues have found multiple genetic variations in the beta-1 adrenergic receptor and have studied these variations in cells, in genetically altered mice and in multiple human trials. As a result of this work, two patents have been issued, five others have been submitted, and five clinical trials have been conducted. The results of these studies show that the genetic variations can predict who will develop failure, provide an indication of disease progression, predict who will require a cardiac transplant, and predict the response to beta-blockers. These genetic variants represent the first genetically-based diagnostic, prognostic and pharmacogenetic tests for heart failure. Additional trials are currently being conducted to further establish these uses.
With asthma and heart failure, other genes are involved in defining these diseases and their treatment response. As these new genes are found, variants will be sought, and then laboratory and human clinical trials will be undertaken.
Dr. Liggett and his colleagues will work with the Computational Medicine Center to develop genotyping assays; correlate genotypes to the clinical endpoints of choice with specialized software; use microarray technology and specialized software to identify new genes; sequence these novel genes to find new variants; and support small-scale clinical trials.
The research is supported by funding from the National Institutes of Health (NIH).