Researchers at UC Davis Health have developed a simple technique to predict how preclinical drugs may affect heart rhythm. The team created a computer model that can be used to screen drugs for unexpected cardiac side effects, particularly heart arrhythmia risk.
Heart rhythm problems, also known as arrhythmias, arise when the electrical impulses that coordinate the heartbeat are not working properly. This causes the heart to beat too fast, too slow, or irregularly. Arrhythmias can cause life-threatening effects such as lack of blood flow and subsequent damage to major organs.
Professor Colleen E. Clancy, lead author of the UC Davis study, is a renowned expert in using high-performance computing to understand electrical changes in the heart.
“One main reason for a drug being removed from the market is potentially life-threatening arrhythmias,” said Professor Clancy. “Even drugs developed to treat arrhythmias have ended up actually causing them.”
The problem, she explained, is that there is no easy way to preview how a drug will interact with hERG-encoded potassium channels essential to normal heart rhythm.
“So far there has been no surefire way to determine which drugs will be therapeutic and which will be harmful,” said Professor Clancy. “What we have shown is that we can now make this determination starting from the chemical structure of a drug and then predicting its impact on the heart rhythm.”
The computer model analyzes the chemical formula of a specific drug to evaluate how it will interact with hERG channels, cardiac cells, and heart tissue. The information can be compared to electrocardiogram (ECG) data from clinical trials for validation.
To test the reliability of their new model, the researchers focused on two drugs that are known to interact with hERG channels. When the computer data was compared with ECGs of patients who were taking the two drugs, the results showed that the predictions from the computer model were accurate.
Professor Clancy expects that the model will provide an essential pre-market test of cardiac drug safety. The technique may ultimately be used to test drug safety for other organs as well, such as the liver and brain.
“Every new drug needs to go through a screening for cardiac toxicity, and this could be an important first step to suggesting harm or safety before moving on to more expensive and extensive testing,” said Professor Clancy.
The study is published in the journal Circulation Research.
By Chrissy Sexton, Earth.com Staff Writer