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Tarantula venom could be a new source for healing


Wed Dec 15, 7:18 AM ET
Top Stories - USATODAY.com


By Justin Dickerson, USA TODAY
And you thought tarantula venom was a bad thing. Not always, according to researchers who have isolated a substance in the spider's venom that could lead to drug treatments for conditions as diverse as muscular dystrophy, urinary incontinence and cardiac arrhythmias.
Scientists at the University at Buffalo have shown that a natural compound called GsMTx4 found in the venom can block channels through the membrane walls of cells. Specifically, it blocks channels that are opened by a stretching in the surface of cell membranes. These "stretch-sensitive" channels are an unusual part of cell biology.
They also are an important one, because these channels let calcium into the cell. Calcium plays an important role in tissue. It is involved in such functions as the heart and bloodstream's response to blood pressure changes as well as the filling of hollow organs such as the bladder. But when the channels become hyperactive - spending more time open than closed - they can cause health problems.
Fred Sachs, professor of biophysics in the university's Center for Single Molecule Biophysics, and his research team discovered recently that the mirror image of GsMTx4 can prevent a cell from undergoing dangerous stretching.
After experimenting with venoms from scorpions, centipedes and spiders, Sachs says the research team (none of whom report being afraid of the creepy crawlers) found through "pure luck" that the compound in the venom of the Chilean Rose tarantula worked to numb these mechanical senses in cells - the same effect that an anesthetic has on the body.
The Chilean Rose tarantulas used in Sachs' research are about 6 inches across. They are harmless, he says, and are sold in the USA as pets. The rare bite someone might get from one feels like a bee sting, he says. (Related story: Spiders catch itsy-bitsy girl's interest)
"Nature doesn't give up its secrets very easily," Sachs says. "She's a rather private individual, and to keep asking these questions is a challenge to no end."
Decades of exploration
Almost two decades ago, researchers in Sachs' lab discovered sensors present in all cells that can detect when they are being stretched. Stretch-sensitive channels in the heart are attuned to the level of blood pressure and begin to malfunction when the pressure is high. This leads to the deterioration of normal heart function, such as cardiac arrhythmias and congestive heart failure.
Although Sachs believed these sensors could hold the key to preventing a number of conditions, no drug had been developed which could react with them to disable the cell's dangerous stretching ability.
Controlling high blood pressure over the long term is helpful, but finding a way to decrease the heart's response to the pressure would be the most useful therapy in these acute situations, says Thomas Suchyna, a researcher at the biophysics center.
People with muscular dystrophy have a mutation that weakens muscle cells so that the cell membrane damages easily when exposed to normal contracting and stretching of the muscle, Suchyna says. The damaged cells can no longer control the tension in the membrane during contraction, and the stretch channels become hyperactive. This can lead to cell death and atrophy of the muscle over time.
But the scientists made a significant advance toward treating these and other conditions when Suchyna and colleague Philip Gottlieb synthesized a "mirror image" version of GsMTx4 that, unlike the original version, might be indigestible by the body. And it was found to alleviate the hazardous stretch responses.
Suchyna says the compound has been shown in two recent studies to reduce the chance of atrial fibrillation in rabbits and muscular dystrophy in mice by decreasing the calcium overload in cells.
Proving that it will work as a drug is still a few years off, but the results are promising, Sachs says. The notion of using "spider spit" to benefit mankind shows "how basic research that doesn't appear to have any practical application can often provide the most unexpected results."
The research was supported by grants from the National Institutes of Health (news - web sites). And Sachs' lab was awarded a $900,000 grant from the Buffalo-based John R. Oishei Foundation that will allow the team to continue its research.

Among the areas of exploration for the researchers is the environment around the stretch-sensitive channels and the possible mutation of GsMTx4 to make it specific for different tissues.
 
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