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

More articles from Life Sciences:

nachricht Russian scientists show changes in the erythrocyte nanostructure under stress
22.02.2019 | Lobachevsky University

nachricht How the intestinal fungus Candida albicans shapes our immune system
22.02.2019 | Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: (Re)solving the jet/cocoon riddle of a gravitational wave event

An international research team including astronomers from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has combined radio telescopes from five continents to prove the existence of a narrow stream of material, a so-called jet, emerging from the only gravitational wave event involving two neutron stars observed so far. With its high sensitivity and excellent performance, the 100-m radio telescope in Effelsberg played an important role in the observations.

In August 2017, two neutron stars were observed colliding, producing gravitational waves that were detected by the American LIGO and European Virgo detectors....

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Global Legal Hackathon at HAW Hamburg

11.02.2019 | Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

 
Latest News

JILA researchers make coldest quantum gas of molecules

22.02.2019 | Physics and Astronomy

Understanding high efficiency of deep ultraviolet LEDs

22.02.2019 | Materials Sciences

Russian scientists show changes in the erythrocyte nanostructure under stress

22.02.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>