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Scorpions are feared not only for their threatening appearance but also because of their highly toxic venom. Yet Tel Aviv University researchers now suggest that this venom could be used to replace opiate-derived painkillers such as morphine, which can be addictive and dangerous.
Plant science Prof. Michael Gurevitz is looking into developing a novel painkiller based on natural compounds found in scorpion venom. As these peptide compounds have evolved over millions of years, some of them show high efficacy and specificity for certain components of the body with no side effects, says Gurevitz.
The toxins found in scorpion venom interact with sodium channels in the nervous and muscular systems, and some of these sodium channels communicate pain, says Gurevitz.
“The mammalian body has nine different sodium channels, and only a certain subtype delivers pain to the brain. We are trying to understand how toxins in the venom interact with sodium channels at the molecular level and particularly how some of the toxins differentiate among channel subtypes.”
“If this is understood, scientists may be able to slightly modify such toxins, making them more potent and specific for certain pain mediating sodium channels,” Gurevitz continues.
With this information, engineering of chemical derivatives that mimic the scorpion toxins would provide novel painkillers of high specificity that have no side effects.
Gurevitz is concentrating on the Israeli yellow scorpion, one of the most toxic scorpions in the world. Its venom contains more than 300 peptides, of which only a fraction has been explored. The reason for working with this venom, he says, is the large arsenal of active components such as the toxins that have diversified during hundreds of millions of years under selective pressure.
During that process, some toxins have evolved with the capability to directly affect mammalian sodium channel subtypes whereas others recognize and affect sodium channels of invertebrates such as insects. This deviation in specificity is for us a lesson of how toxins may be manipulated at will by genetic engineering, he says.
While it may seem odd to use scorpion venom to treat some body disorders, this counterintuitive usage is already familiar from the use of botulin toxin for treating tics and excessive sweating, as well as temporarily relaxing wrinkles.
The Chinese recognized the effectiveness of scorpion venom hundreds of years ago, and still use it, believing it to have powerful analgesic properties, the TAU researcher says. Some studies have shown that scorpion venom can also be used to treat epilepsy.
“We study how these toxins pursue their effects in the Western sense to see how it could be applied as a potent painkiller,” he said.
Using an approach called “rational design” or “bio-mimicry,” Gurevitz is trying to develop painkillers that mimic the venom’s bio-active components. The idea is to use nature as the model, and to modify elements of the venom so that a future painkiller designed according to these toxins could be as effective as possible, while eliminating or reducing side effects.
Finding a new and effective pain medication could solve one of the biggest problems in the medical world today. Pain is an important physiological response to danger, physical injury and poor health, yet doctors need to reduce extreme pain in patients that aspirin can’t relieve.
To date, opiate-derived painkillers have been quite effective, but the medical community is eager to find other solutions due to the risks associated with their use.
“This new class of drugs could be useful against serious burns and
cuts, as well as in the military and in the aftermath of earthquakes
and natural disasters,” Gurevitz said.
“Instead of running the risk of addiction, this venom-derived drug,
mimicking the small peptide toxin, would do what it needs to do and
then pass from the body with no traces or side-effects.”