Featured Research

from universities, journals, and other organizations

Two-gene test predicts which patients with heart failure respond best to beta-blocker drug

Date:
October 16, 2012
Source:
University of South Florida (USF Health)
Summary:
A landmark paper identifying genetic signatures that predict which patients respond to a life-saving drug for congestive heart failure has just been published. Medical researchers discovered and characterized the two genetic variations that determine how patients are likely to respond to the beta-blocker bucindolol.

A landmark paper identifying genetic signatures that predict which patients will respond to a life-saving drug for treating congestive heart failure has been published by a research team co-led by Stephen B. Liggett, MD, of the University of South Florida.

The study, drawing upon a randomized placebo-controlled trial for the beta blocker bucindolol, appears this month in the international online journal PLoS ONE. In addition to Dr. Liggett, whose laboratory discovered and characterized the two genetic variations, Christopher O'Connor, MD, of Duke University Medical Center, and Michael Bristow, MD, PhD, of ARCA biopharma and the University of Colorado Anschutz Medical Campus, were leading members of the research team.

Dr. Stephen Liggett, who joined USF just four months ago to lead the University's Center for Personalized Medicine and Genomics, was a senior author of the paper.

The analysis led to a "genetic scorecard" for patients with congestive heart failure, a serious condition in which the heart can't pump enough blood to meet the body's needs, said Dr. Liggett, the study's co-principal investigator and the new vice dean for research and vice dean for personalized medicine and genomics at the USF Morsani College of Medicine.

"We have been studying the molecular basis of heart failure in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," Dr. Liggett said. "We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with heart failure who will not respond to bucindolol and those who have an especially favorable treatment response. We also identified those who will have an intermediate level of response." The research has implications for clinical practice, because the genetic test could theoretically be used to target the beta blocker to patients the drug is likely to help. Equally important, its use could be avoided in patients with no likelihood of benefit, who could then be spared potential drug side effects. Prospective studies are needed to confirm that bucindolol would be a better treatment than other classes of beta blockers for a subset of patients with health failure.

Dr. Liggett collaborated with medical centers across the United States, including the NASDAq-listed biotech company ARCA biopharma, which he co-founded in Denver, CO. This genetic sub-study involved 1,040 patients who participated in the Beta-Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for heart failure exacerbations and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," Dr. Liggett said.

The genetic test discovered by the Liggett team requires less than 1/100th of a teaspoon of blood drawn from a patient, from which DNA is isolated. DNA is highly stable when frozen, so a single blood draw will suffice for many decades, Dr. Liggett said. And since a patient's DNA does not change over their lifetime, as new discoveries are made and other tests need to be run, it would not be necessary to give another blood sample, he added.

This is part of the strategy for the USF Center for Personalized Medicine and Genomics. The discovery of genetic variations in diseases can be targeted to predict three new types of information: who will get a disease, how the disease will progress, and the best drug to use for treatment.

"In the not too distant future, such tests will become routine, and patient outcomes, and the efficiency and cost of medical care will be impacted in positive ways. We also will move toward an era where we embrace the fact that one drug does not fit all," Dr. Liggett said. "If we can identify by straightforward tests which drug is best for which patient, drugs that work with certain smaller populations can be brought to the market, filling a somewhat empty pipeline of new drugs."

This approach is applicable to most diseases, Dr. Liggett said, but the USF Center has initially concentrated on heart disease, because it is a leading cause of deaths, hospitalizations and lost productivity in the Tampa Bay region and Florida. Dr. Liggett is a recent recruit to the USF Health Morsani College of Medicine, coming from the University of Maryland School of Medicine. His work at USF has been supported by several National Institutes of Health grants and $2 million in funding from Hillsborough County.

Heart failure is characterized by an inability of the heart muscle to pump blood, resulting in dysfunction of multiple organs caused by poor blood and oxygen flow throughout the body. An estimated 6 million Americans are living with heart failure, and more than half a million new cases are diagnosed each year. About 50 percent of patients diagnosed with heart failure die within five years. The economic burden of heart failure in the United States is estimated at $40 billion a year.


Story Source:

The above story is based on materials provided by University of South Florida (USF Health). Note: Materials may be edited for content and length.


Journal Reference:

  1. Christopher M. O'Connor, Mona Fiuzat, Peter E. Carson, Inder S. Anand, Jonathan F. Plehn, Stephen S. Gottlieb, Marc A. Silver, JoAnn Lindenfeld, Alan B. Miller, Michel White, Ryan Walsh, Penny Nelson, Allen Medway, Gordon Davis, Alastair D. Robertson, J. David Port, James Carr, Guinevere A. Murphy, Laura C. Lazzeroni, William T. Abraham, Stephen B. Liggett, Michael R. Bristow. Combinatorial Pharmacogenetic Interactions of Bucindolol and β1, α2C Adrenergic Receptor Polymorphisms. PLoS ONE, 2012; 7 (10): e44324 DOI: 10.1371/journal.pone.0044324

Cite This Page:

University of South Florida (USF Health). "Two-gene test predicts which patients with heart failure respond best to beta-blocker drug." ScienceDaily. ScienceDaily, 16 October 2012. <www.sciencedaily.com/releases/2012/10/121016103915.htm>.
University of South Florida (USF Health). (2012, October 16). Two-gene test predicts which patients with heart failure respond best to beta-blocker drug. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/10/121016103915.htm
University of South Florida (USF Health). "Two-gene test predicts which patients with heart failure respond best to beta-blocker drug." ScienceDaily. www.sciencedaily.com/releases/2012/10/121016103915.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins