Rare heart defect reproduced in petri dish, hope for cure

By Dr. Ananya Mandal, MDFeb 13 2011

U.S. researchers have created beating heart cells in the lab with the same heart defect using skin cells taken from children with a rare heart defect. This means they can now test new drugs in human cells instead of mice.

The team led by Ricardo Dolmetsch of Stanford University reported on Wednesday in the journal Nature that heart drugs did not work but a cancer drug being studied by Cyclacel Pharmaceuticals Inc appears to help. This new technology used for the first time can create human models of disease by reprogramming ordinary cells to behave like embryonic stem cells that can give rise to any tissue in the body. Dolmetsch said, “Because every cell in our body has the same genetic programming, that means we can take skin cells and reprogram them to generate stem cells, and we can take those cells to make heart cells.” The technique was developed in 2006. These induced pluripotent stem cells or iPS cells can be collected from people with genetic diseases and grown in batches that live for months and years in the lab.

For this study the team collected skin cells from children with Timothy syndrome - a rare heart condition in autistic children. These children have an irregular heart rhythm. Dolmetsch said, “We generated these reprogrammed cells from these kids and over the last four years or so we developed these methods for converting these cells into cardiac cells.” Next, the team tested several heart rhythm drugs to see if they corrected the problem. None worked, but they did have success with the experimental cancer compound roscovitine, now being tested in phase 2 trials.

“The potential is really large,” he said. He added that several drugs that can lead to heart rhythm defects can be tested for toxicity using this model. “You can’t go into the heart of a sick little boy or girl and take the cells out to study what's going on…And mice are not a good model, because their hearts are very different,” he explained.

Stanford has applied for patents on the technology and Dolmetsch said several drug companies, including Pfizer, Roche and Amgen, have expressed interest in licensing some of the lines. The study was funded by the National Institutes of Health, the Simons Foundation, the Japan Society for the Promotion of Science, the American Heart Association Western States, and Mrs. Linda Miller, Ben and Felicia Horwitz and Mr. and Mrs. Michael McCafferey.