Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Snake venom reveals clues about heart drug

17.08.2004


With the help of snake venom and sophisticated laboratory testing, scientists believe they’ve uncovered the reason why a group of new heart medications were doing some patients more harm than good. Researchers from Wake Forest University Baptist Medical Center and colleagues report the findings in the current on-line issue of The Journal of Molecular Biology.



"Our findings suggest that drug developers should take a different approach," said Roy Hantgan, Ph.D., principal investigator, "and we’ve also developed a way to test drugs for these harmful effects before they are given to patients."

Hantgan, an associate professor of biochemistry, and colleagues studied a group of drugs called integrin antagonists that are designed to prevent blood clots from forming and causing a heart attack during angioplasty, a procedure that uses a balloon-like device to clear narrowed heart arteries.


Intravenous forms of the drug, including ReoPro®, proved very effective at minimizing complications of angioplasty in most patients. Drug manufacturers then worked to make oral forms, so the benefits could be extended after patients left the hospital. But research trials for three different oral drugs were stopped after early results showed a 33 percent increase in patient deaths – with no clear cause. Researchers were unsure what caused the disparity – the intravenous drug was beneficial, while the oral form could be deadly.

Integrin antagonists are designed to block a natural clotting mechanism. They target a protein on blood platelets called an integrin. Integrins, which have been described as the "glue of life," are essential for clotting. The process begins when integrin receptors combine with fibrinogen, a protein in the fluid part of blood. The platelets then congregate at the site of an injury to stem blood loss.

During angioplasty, however, this clotting mechanism can result in a heart attack. When a piece of plaque buildup breaks off in an artery, or when the angioplasty balloon crushes plaque buildup, integrin receptors are activated, which can cause a blood clot to block the artery. Integrin antagonists were designed to prevent this response – the drugs combine with the integrin receptors so that fibrinogen isn’t able to.

In trying to solve the mystery of why one type of integrin antagonists works better than another, Hantgan and colleagues decided to enlist the help of a protein found in snake venom that binds to the integrin and blocks fibrinogen. This causes rapid bleeding in the snake’s prey.

"We wanted to look at a natural protein to see how the synthetic drugs might work," Hantgan said.

Using the electron microscope and laboratory tests that measure the size and shape of very small proteins, the team discovered that the snake venom protein blocks the receptors, just as the drugs do. But after the protein is withdrawn, some of the receptors remain activated, creating the potential for clotting.

"Likewise, the drugs are effective at blocking the receptor, but some of the newer drugs also cause the receptor to remain activated," said Hantgan. "The beneficial effects of these drugs seem to be inseparable from their side effects."

The team tested several integrin antagonists and found that all, including the newer, oral medications, had the response in varying degrees. Hantgan speculated that dips in patients’ drug levels that can occur with oral medications could leave them especially vulnerable to the integrin-activating effects.

"This result suggests that no matter how good a drug you develop, you’re going to have this problem in some patients," said Hantgan. "We believe that drugs that are designed to bind to integrin receptors inside the platelet, rather than on the surface, might have a better chance of working."

Karen Richardson | EurekAlert!
Further information:
http://www.wfubmc.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Epoxy compound gets a graphene bump

14.11.2018 | Materials Sciences

Microgel powder fights infection and helps wounds heal

14.11.2018 | Health and Medicine

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>