Dangerous cardiac side effects are a major cause of drug trial failures and recalls of marketed drugs. Pharmaceutical companies and the U.S. Food and Drug Administration (FDA) have a common interest in identifying and eliminating drugs that have potential cardiac toxicities before they are tested in patients. The Small Business Innovation Research (SBIR) program of the National Heart, Lung, and Blood Institute (NHLBI) has been at the forefront of supporting research on developing novel tests to assess the heart safety of new drug candidates. Cleveland-based ChanTest, now a part of Charles River Laboratories, received more than $2 million of SBIR funding from the NHLBI to develop such tests as well as to advance a new drug to treat atrial fibrillation.
Scientist conducts an experiment evaluating the hERG ion channel, an important benchmark in evaluating cardiac risk in preclinical drug development. Photo credit: Charles River Laboratories
Emergence of ChanTest
Founded in 1998, ChanTest focused on the study of ion channels, which are pores within the cell membrane that facilitate the transport of key chemicals across the cell. These protein-based channels play a key role in the normal operation of nerve, heart, muscle, and other cells. Over the years, ion channels have become targets of intense interest for assessing the potentially toxic effects of new drugs before they are tested in humans.
Developing new drug safety tests with NHLBI SBIR funding
ChanTest received its first SBIR grant from the NHLBI in 1998. The company, which was acquired by Charles River Laboratories in 2014, has received a total of eight SBIR awards. Its initial SBIR award focused on the study of the human ether-a-go-go related gene (hERG), which codes for a potassium ion channel that is critical for normal heart muscle operation, particularly the electrical activity that controls the heartbeat.
The scientists that founded ChanTest were among the first to demonstrate that certain drugs can cause sudden cardiac death by blocking the hERG potassium ion channel. They pioneered hERG channel testing to identify drugs with this effect. With NHLBI SBIR funding, Chan Test developed several commercial lab tests that can identify drug candidates with the potential to disrupt normal heart muscle function.
Today, the assays developed by these scientists play a key role in both drug safety testing and drug discovery worldwide. The FDA now requires the hERG assay to be completed as part of an Investigational New Drug (IND) submission as an indicator of potential cardiac toxicity. Research like this has the potential to improve health and save millions of dollars annually by reducing the recall of cardiotoxic drugs. These efforts could also improve the safety of drugs in development, and increase the efficiency of drug development by allowing companies to focus on the safest, most promising drug candidates.
Scientist prepares a compound to evaluate its potential for causing heart problems. Photo credit: Charles River Laboratories
The SBIR-supported work of ChanTest has already had a tremendous impact on people’s everyday lives. Among its many achievements, the research has:
- Pioneered testing of the hERG channel to identify drugs that can cause sudden cardiac death;
- Conducted safety testing of more than 30,000 compounds; and
- Developed an extensive library of ion channel-expressing cell lines.
More about the NHLBI SBIR and STTR programs
The NHLBI Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support research and development on the next generation of commercially promising technologies and products to prevent, diagnose, and treat heart, lung, blood, and sleep-related diseases and disorders. For more information on NHLBI’s small business programs, visit http://www.nhlbi.nih.gov/research/funding/sbir/about-program
Reference to any specific commercial products, process, service, manufacturer, and/or company does not constitute an endorsement or recommendation by the National Heart, Lung, and Blood Institute (NHLBI), the NHLBI's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, or any other portion of the U.S. Government.