Monday, May 21, 2018
Health

USF to begin analyzing patient genetics at new Heart Institute

TAMPA — A simple blood test is launching the University of South Florida's ambitions to become a leader in treating heart disease, the nation's No. 1 killer.

That's all it takes to run the genetic tests that USF leaders hope to translate into medical advancements at their proposed $50 million USF Heart Institute, whose development is under way with $9 million in tax money.

The results could help doctors, for example, select the best drug for patients suffering from heart failure, a slow killer for which treatment can be a guessing game. That's the promise of new research by USF's Dr. Stephen Liggett, who has identified a pair of genetic signatures helpful in predicting the effectiveness of a certain beta-blocker drug.

Early next year, a new partnership between USF and the American College of Cardiology aims to expand on this type of genetic discovery. The groups plan to work together on a clinical trial to sequence the DNA of 1,000 Tampa patients. It's a test run for larger efforts to link patient genetic information with a database of clinical information.

The goal is to create new therapies for cardiac patients based on their unique genetic makeup.

"It's a ripe area of research," said Dr. William Oetgen, a professor at the Georgetown University School of Medicine and the ACC's senior vice president of science and quality. "We don't know where it's going to go, or what discoveries are going to be made. "

•••

The Heart Institute is a top priority for USF's medical school. This spring, state legislators launched it with $6.9 million in tax money, allowing USF to start the design of a 100,000-square-foot research building on its main campus in north Tampa.

Hillsborough County commissioners awarded $2 million more. University officials hope to break ground in July on the institute, which is expected to employ at least 56 people making an average of $76,000 annually.

Researchers will seek to identify genetic markers that indicate which patients are predisposed to heart disease, so they can be targeted for early intervention. And they will test emerging stem cell therapies that could help repair heart damage.

The work also will build on research like the recently published work of Liggett, USF's new vice-dean for personalized medicine and genomics.

While in his previous post at the University of Maryland, he helped lead a national team of investigators examining genetic markers to improve treatment of heart failure. The researchers sought to identify which patients are most likely to respond to bucindolol, one of about a dozen beta-blockers on the market.

About half of U.S. patients diagnosed with heart failure — when the heart can't pump enough blood and oxygen to support the body's organs — die within five years. Physicians have a narrow window to get patients started on the right treatment, Liggett said, because it can take a year for drugs to take effect.

"In heart failure, we have a substantial problem, because we are unable to determine who is going to respond to what drugs," he said. "We are in a situation that some have called trial and error."

The study, published in the journal PLoS One, followed about 1,000 patients for five years. While they were receiving treatment, researchers analyzed their genetics, identifying a pair of genetic signatures predictive of a strong response to bucindolol.

These findings have been used to develop a blood test to help doctors know which patients are likely to get better on the medication from the beginning of their treatment course, Liggett said.

It's the kind of development that could make a difference to Roger Ramey. The 59-year-old Citrus Park man had a heart attack in 2006 and later was diagnosed with heart failure, which can develop after heart attacks. Finding the right medication regimen has been an ongoing struggle.

"Every time I'd go in the hospital, they wanted to mess with that," said Ramey, a USF patient, who feels weak and short of breath when his drug levels are off. "I wouldn't have gone through all the times where they were guessing on the dosage."

•••

The next step for USF is to prove its ability to carry out genetic testing on a large scale — and marry the results to a rich database of patient clinical information maintained by the American College of Cardiology.

That's the goal of a joint clinical trial to begin at USF early next year.

"It's proof of concept. It's never been done," said Dr. Leslie Miller, director of the USF Heart Institute.

He said success could result in national expansion of the study to involve thousands of patients. The end goal is "developing whole new therapeutics based entirely off of the correlation of genomic findings and the clinical database," Miller said.

To participate, cardiac patients would have to agree to have two tubes of blood drawn for DNA sequencing. The results would be confidential, Miller said. Participating patients would get to be the first to try out any new therapies developed.

The concept is similar to M2Gen, a for-profit startup of Moffitt Cancer Center, which also seeks to develop new drugs from its large database of frozen tumor samples. Yet M2Gen, a collaboration with pharmaceutical giant Merck & Co., so far hasn't generated the blockbuster drugs that some envisioned when it was announced in late 2006.

And using patient genetics to tailor cancer treatments is much farther along, said Oetgen of the national cardiologists' society.

"The likelihood of finding a blockbuster drug or discovery is higher in oncology, because they are dealing with literally life and death situations over very short time frames," Oetgen said.

In cardiac care, "it's likely that patients will benefit," he added. "But the scale and the magnitude of the benefit is to be determined."

Letitia Stein can be reached at [email protected] or (727) 893-8330.

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