Cardiotoxicity is defined as damage or dysfunction occurring in the heart as a result of exposure to a chemical substance. Cardiotoxicity is one of the major reasons given when the development of a drug fails or a drug is withdrawn from the market. With the cost of bringing a new drug to market averaging $2.6 billion USD, there are pressing ethical and economic reasons to find a faster, more accurate way to predict cardiotoxicity.
Developments announced in the last few weeks are encouraging. UC Berkeley researchers led by Professor Kevin Healy published a study of their functional “heart-on-a-chip:” a 3-dimensional network of adult stem cell-derived heart muscle cells linked together on a microfluidic platform that reproduces blood flow. The cells beat normally, and responded appropriately to the effects of four well-described heart drugs (isoproterenol, E-4031, verapamil and metoprolol). According to Healy, “Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy.” (See the open-access paper here.)
In addition, NC3Rs recently awarded its 2014 3Rs prize to Oliver Britton, a PhD student who created an innovative computational model of cardiac electrophysiology. Because the model incorporates within-species variations in heart properties (which are usually averaged in more simplistic models), it has the potential to more accurately identify potentially toxic drug compounds – allowing them to be pulled from development before animal studies begin. Quoted in the NC3Rs press release, Professor Ian Kimber said of the model: “Mr Britton’s paper really stood out to the panel because of (its) potential as a replacement for early-stage animal tests in drug safety studies, across a broad range of disciplines. The model has also been developed into a piece of user-friendly software, encouraging uptake and use by industry, which could have an important impact on the reduction of animals in research.”
Human-relevant alternative models such as these have the potential to reduce the cost, time, and numbers of animals expended in drug development, while increasing human safety.
Watch video of the beating UC Berkeley “heart-on-a-chip”: