I’ve discussed before the fact that one of the most common reasons a previously approved drug is pulled from the marketplace is the discovery — after it’s been cleared for use in people — that it causes heart damage. This happens because the animal models used to test a drug’s safety aren’t great mimics of how human hearts work.
Stanford cardiologist Joseph Wu, MD, PhD, has been working on ways to use induced pluripotent stem cells to generate human heart muscle cells for study in the laboratory, giving reliable, non-invasive access to heart tissue. In a new paper, he and his colleagues showed how they used these heart cells to test the effect of various members of a class of chemotherapy drugs called tyrosine kinase inhibitors on the cells’ ability to beat rhythmically and effectively, respond appropriately to electrophysiological signals and to communicate with one another.
As I explained in our release on the research, which appears in Science Translational Medicine:
The researchers found that their assay can accurately identify those tyrosine kinase inhibitors already known to be the most dangerous in patients. In the future, they believe their system may prove useful in the early stages of drug development to screen new compounds for cardiotoxicity.
Validating the researchers’ cardiac-safety test on drugs with extensive clinical track records is necessary before the assay can be used to predict with confidence the likely clinical outcomes of drugs still under development.
The researchers used their findings to create a kind of scorecard of “cardiac safety indices” for 21 tyrosine kinase inhibitors. Drugs known to be particularly dangerous to heart function, such as nilotinib, which is approved for the treatment of chronic myelogenous leukemia, and vandetanib, which is approved for the treatment of some types of thyroid cancer, garnered the lowest safety indices based on the assay; conversely, those known to be better tolerated by patients ranked higher on their safety index.
Wu is director of the Stanford Cardiovascular Institute and a member of the Stanford Cancer Institute. When explaining the significance of the study to me, he said, “This type of study represents a critical step forward from the usual process running from initial drug discovery and clinical trials in human patients. It will help pharmaceutical companies better focus their efforts on developing safer drugs, and it will provide patients more effective drugs with fewer side effects.”
Previously: Predicting chemo-induced heart damage using iPS cells, Stem cells create faithful replicas of native tissue, according to Stanford study and “One of the most promising minds of his generation”: Joseph Wu takes stem cells to heart
Photo by Steve Fisch