Monday, March 25, 2013

Stem cells in a dish reveal drug’s toxic side

Frozen iPS cells, Photo courtesy of William Collins in the lab of Deepak Srivastava at the Gladstone Institutes
When the discovery of reprogrammed stem cells, so-called iPS cells, won the Nobel Prize last October, these versatile cells were generally portrayed as offering the promise of changing medicine in the distant future. But in reality they are having an impact today. This is not through cells being given to patients but rather as research tools helping to find new drugs and to sort out toxic from non-toxic drug candidates.

My colleagues and I have written about using iPS cells as disease-in-a-dish models before (see blog entries here). Now, a CIRM-funded team at Stanford has proven that heart cells grown from iPS cells can be used to detect drug toxicity.

Experts have assumed this would be possible, and most major drug companies are investing in iPS research assuming it is possible. Here we have a great example of a known drug toxicity being verified through a disease-in-a-dish.

The team lead by Joseph Wu took skin samples from three family members who had inherited a faulty heart rhythm and one who did not inherit the defect. They made iPS cells from those skin samples and turned those into beating heart tissue in a dish. There they saw differences in function between those cells with the defect and the ones without it.

They then tested three drugs on these cells, one that has been shown to be safe, one that has some toxicity in certain patients, and one that was pulled from the market in 2000 because it was causing deaths. In each case the cells in the dish verified what had been seen in patients. But with the sometimes-lethal drug, they were able to show that the effect depended on dose. This information could have given the manufacturer the chance to alter the way the drug was used and prevent the deaths.

A press release from Stanford quoted Wu about the research that was published in Circulation:
“This study shows that the use of patient-specific stem cells to detect cardiotoxic properties of pharmaceutical compounds may be more accurate than the current drug-safety assays mandated by the FDA. We are also able to demonstrate disease-specific responses to cardiotoxic drugs. We believe that, in the future, this may become a standard way to test drug safety and efficacy.”
The Stanford team speculated that this use of iPS cells could save millions of dollars in developing new drugs. This is one reason why CIRM invested $32 million last week to develop an iPS cell bank that will have some 9,000 cells lines from 3,000 patients with 11 different diseases (we wrote about that initiative here). Wu, who led the research, received one of the awards to develop cell lines that we'll be storing in the bank.


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