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Help for enlarged hearts?

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About one in 500 people have a genetic mutation that too often first shows up tragically when a young athlete dies suddenly on a basketball court or football field. The mutation causes their hearts to change shape, making them weaker and less able to pump blood. It also makes some people’s heart develop abnormal heartbeats. It’s those faulty heart rhythms that can harm athletes with the condition.

Even when a family knows they carry one of the mutated genes linked to the condition, called hypertrophic cardiomyopathy, they cannot intervene medically. Their only choice has been to bench the athlete. Because no one knew why the heart was behaving the way it was, researchers didn’t know where to target any intervention. Now, that has changed.

A CIRM-funded team led by Joseph Wu at Stanford made ingenious use of a technique we have written about often here, the ability to use reprogrammed stem cells known as iPS cells to created a disease-in-a-dish model of the condition. They started with skin samples from all 10 members of a family in which the mother and four children carried one of the mutations, and the father and other four children did not. They turned those cells into iPS cells and then directed them to become heart muscle cells known as cardiomyocytes.

In their press release, Stanford quotes Wu talking about the value of studying diseases using iPS cells:

“For obvious reasons, it’s difficult to get primary human heart tissue from living patients for study. Moreover, animal hearts are not ideal substitutes either because they contract differently and have a different composition than human hearts. As a result, it has been difficult to show the specific cause of heart failure, whether it’s due to enlargement of the organ or if it’s caused by abnormalities at the single-cell level.”

The research highlights what many experts consider to be some of the main advantages of iPS cells — the ability to quickly create patient-specific cells of nearly any tissue type for study, as well as to allow rapid and safe drug screening.

In the work published in Cell Stem Cell January 3, they found that the cells from all 10 family members behaved normally at first. But after about 30 days in culture the cells carrying the mutation started to have an abnormal buildup of calcium, which plays a key role in how heart muscle beats. This finding became an immediate target for potential therapy. And the beauty of the disease-in-a-dish model is researcher can test potential drugs on the beating cells in the laboratory and rapidly narrow their search for candidate therapies.

CIRM’s Senior VP for Research and Development, Ellen Feigal, is quoted in an article about the work in the San Francisco Chronicle today on the power of using these cells in this way.

“Using these human cells from the patient can actually lead us to a better understanding of the disease, and if we have a better understanding of the disease and if we can identify key targets, then we have the potential to develop interventions.”

The power of the disease model in this previously untreatable disease was also noted in the Chronicle by Cesar Molina, a spokesman for the American Heart Association:

“It opens up a door for pharmaceutical development that hasn’t been there.”

We expect to be writing more stories about the power of iPS cells in the coming year.

D.G.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

Learn more about the California Institute for Regenerative Medicine



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