This last winter has been a tough one for my small rural community. Every time I turned around, more people were sniffling and sneezing, coughing and feverish. We've all been just as likely to compare doctors' recommendations as our children's report cards, and more than one of my friends walked away from the physician with a prescription for a Z-pack: a five-day regimen of an antibiotic called Zithromax that's effective in treating many common infections.
Last week, however, the Food and Drug Administration strengthened their warning about Zithromax: Mounting evidence has shown that the drug can be dangerous for people with certain preexisting heart conditions, or those who may be taking other drugs that affect the heart's rhythm.
How could such a common medication carry such risks? It's simple, explain Stanford scientists. The current methods of testing a prospective new drug's heart safety profile depend primarily on the use of non-heart cells that are genetically modified to mimic some aspects of real ones. But they're no substitute for the real thing. Unfortunately, the "real thing" is hard to get. After all, we're not all lining up for heart biopsies so scientists can have a steady supply of material on which to test each drug.
Today cardiologist Joseph Wu, MD, PhD, medical student Andrew Lee, and postdocs Ping Liang, PhD, and Feng Lan, PhD, published some really exciting new work in the journal Circulation (subscription required) that presents an alternative. In short, the researchers collected painless skin samples from patients with one of three inherited cardiac conditions, as well as from healthy family members. They then used induced pluripotent stem, or iPS, cell technology to convert the skin cells in the laboratory into functioning heart cells that reflected each patient's specific heart aliment. Finally, they tested the response of the cells to specific medications - some of which have been shown to be relatively safe for the heart and another that had been withdrawn from the market due to unexpected cardiotoxicity. As Lee explained in our release:
It’s clear that individual patients will respond uniquely to specific drugs. If you have a hereditary disease or a problem with your ion channels, you’re going to respond differently than members of the general population. Even companies relying on genetically normal human embryonic-stem-cell-derived cardiac cells won’t be able to see all these effects. But our ‘clinical trial in a dish’ with patient-specific iPS cells allows us to model this personalized response and identify high-risk groups who should not receive the drug.
The researchers found that the heart cells in the dish responded in much the same way to the medications as did human patients. They anticipate that this type of "clinical trial in a dish" may become a standard method of testing drugs for cardiotoxicity on healthy and diseased hearts. It may also allow researchers and clinicians to test the effect of combinations of drugs while limiting the risk to real patients. Although none of my antibiotic-toting friends have been harmed by Zithromax (and thank goodness, we all seem to be feeling a bit better!), who would argue with better, faster and safer testing of all drugs? According to Wu:
Our hope is that, instead of a physician using a patient as a guinea pig, trying one medication after another until something is found to be effective, this method will one day lead to personalized drug screening to find out exactly which medication is the best for you.
I'm really excited about this research, and in this use for iPS cells in general. We'll likely be hearing more about this approach; earlier this week Wu, who co-directs the Stanford Cardiovascular Institute, received$1.44 million from the California Institute for Regenerative Medicine to collect tissue samples to create iPS cells from several hundred patients with idiopathic familial dilated cardiomyopathy - that is, members of families with a predisposition to develop enlarged and weakened hearts without an obvious cause.
Previously: Sudden cardiac death has a cellular cause, say Stanford researchers, New leaders in heart medicine at Stanford and Lab-made heart cells mimic common cardiac disease in Stanford study
Photo by kaibara87