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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>