Featured Research

from universities, journals, and other organizations

'Smart Gene Therapy' Protects Against Damage From Heart Attack

Date:
August 3, 2004
Source:
Duke University Medical Center
Summary:
Early intervention with a novel kind of "smart gene therapy" might effectively prevent the organ damage commonly suffered by heart attack victims, suggests a new animal study by researchers at Brigham and Women's Hospital in Boston and Duke University Medical Center.

DURHAM, N.C. -- Early intervention with a novel kind of "smart gene therapy" might effectively prevent the organ damage commonly suffered by heart attack victims, suggests a new animal study by researchers at Brigham and Women's Hospital in Boston and Duke University Medical Center. The therapy combines a therapeutic gene with a genetic "sensor" that recognizes and responds to the oxygen deprivation that follows the reduced blood flow, or ischemia, from coronary artery disease and heart attack.

As soon as the oxygen declines, the sensor turns on the therapeutic gene, thereby protecting the heart. In addition to its potential for patients with heart disease, the strategy might also prove useful for any condition in which tissues are susceptible to loss of blood supply, including stroke, shock, trauma and sepsis, the researchers said.

When administered to rat hearts several weeks before ischemia, the designer gene combination protected the heart from much of the damage that may weaken the organ and lead to failure, according to the researchers. Their report will appear in a forthcoming issue of Proceedings of the National Academy of Sciences and in the journal's online edition the week of Aug. 2, 2004.

The finding marks the first time a therapeutic gene complete with a built-in sensor that allows the gene to respond immediately to the condition it treats has been shown to work, said Victor J. Dzau, M.D., chancellor of health affairs at Duke University and an active physician-scientist at Duke. Such a therapy could offer a significant advance over available methods for treating heart patients, which are limited in their ability to provide treatment in the narrow window of time before irreversible heart damage occurs, he said. The work, led by Dzau at Brigham and Women's Hospital prior to his move to Duke in July, was supported by the National Institutes of Health and the Edna Mandel Foundation.

"While drugs that can protect heart muscle are available, most patients barely make it to the hospital in time to take advantage of them," Dzau said. "This smart gene therapy could be administered preemptively to high- risk patients months before they develop a heart attack to provide them with long-term protection from ischemic injury. The minute this gene is switched on following a loss of blood flow, levels of the therapeutic protein rise rapidly, providing near-complete protection."

In patients with myocardial ischemia, the loss of blood flow causes the heart tissue to slowly or suddenly starve of oxygen and other nutrients. Eventually, said Dzau "little bits of heart muscle get chewed away" as tissue dies, weakening the organ and resulting in failure. When blood flow becomes blocked completely, a heart attack can ensue. Physicians may be able to reopen narrow or blocked heart vessels with balloon angioplasty, but delayed restoration of blood flow often leads to inflammation and tissue injury. Ischemia also can occur in arteries of the kidneys, lungs, liver or the brain, where it leads to stroke, he added.

The team developed a "therapeutic gene construct" that contains both DNA sequences that can detect oxygen deficiency and a therapeutic human gene -- heme-oxygenase 1 -- that has been shown to protect cells. They then inserted the gene construct into a harmless virus known as adeno-associated virus, whose job was to transport the therapeutic gene into the genetic material of the rat's cells.

"We're trying to create a physiological on-off switch that will automatically turn on the therapeutic gene when ischemia causes dangerous levels of oxygen deprivation," Dzau said. "Such internal regulation is ideal for safe and effective gene therapy."

The researchers injected the gene construct into the heart, liver and skeletal muscle of rats in the laboratory. Five weeks later, they restricted blood flow to the animals' organs by clamping key arteries for a period of an hour and then examining the organs for evidence of injury.

Inducing ischemia and oxygen deprivation in this way caused a five-fold increase in the therapeutic gene's activity in the heart, the researchers reported. That activity, in turn, resulted in a dramatic reduction in damage to the heart, Dzau said, with a significant 65 percent decrease in tissue death in animals treated with the gene construct compared to control animals. Skeletal muscle and liver exhibited a similar decline in injury following the gene therapy treatment.

In addition, one month later the untreated animals exhibited severe thinning of the heart wall and reduced heart function compared to those that received the gene therapy. After four months, the untreated rats still showed marked thinning of the heart wall, while those treated with the gene construct showed virtually no evidence of damage, Dzau said.

The team will next verify its results in another large animal model. If the findings hold, Dzau predicts the therapy might be ready to enter a phase I clinical trial in human patients in as little as a year. The adeno-associated vector used to insert the gene construct has been shown to be safe for humans through its use in the treatment of hemophilia, noted Dzau.

Collaborators on the research include Alok Pachori, lead author of the study, Luis Melo, Melanie Hart, Nicholas Noiseux, Lunan Zhang, Fulvio Morello, Scott Solomon, Gregory Stahl and Richard Pratt, all of Brigham and Women's Hospital.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "'Smart Gene Therapy' Protects Against Damage From Heart Attack." ScienceDaily. ScienceDaily, 3 August 2004. <www.sciencedaily.com/releases/2004/08/040803100832.htm>.
Duke University Medical Center. (2004, August 3). 'Smart Gene Therapy' Protects Against Damage From Heart Attack. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2004/08/040803100832.htm
Duke University Medical Center. "'Smart Gene Therapy' Protects Against Damage From Heart Attack." ScienceDaily. www.sciencedaily.com/releases/2004/08/040803100832.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 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:
from the past week

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