Prof. Michael Gurevitz of Tel Aviv
University's Department of Plant Sciences is
investigating new ways for developing a novel
painkiller based on natural compounds found
in the venom of scorpions. These compounds
have gone through millions of years of
evolution and some show high efficacy and
specificity for certain components of the body
with no side effects, he says.
Peptide toxins found in scor...pion venom
interact with sodium channels in nervous and
muscular systems -- and some of these
sodium channels communicate pain, says
Prof. Gurevitz. "The mammalian body has
nine different sodium channels of which only
a certain subtype delivers pain to our 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 we figure this out, we may be able to
slightly modify such toxins, making them
more potent and specific for certain pain
mediating sodium channels," Prof. Gurevitz
continues. With this information, engineering
of chemical derivatives that mimic the
scorpion toxins would provide novel pain
killers of high specificity that have no side
effects.
An ancient Chinese secret?
In his research, Prof. Gurevitz is
concentrating on the Israeli yellow scorpion,
one of the most potent scorpions in the
world. Its venom contains more than 300
peptides of which only a minor 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 the use of scorpion venom to treat
some body disorders seems counter-intuitive,
the Chinese have recognized its effectiveness
hundreds of years ago. "The Chinese, major
practitioners of what we call 'alternative
medicine,' use scorpion venom, believing it to
have powerful analgesic properties," Prof.
Gurevitz says. Some studies have also
shown that scorpion venom can 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."
Using an approach called "rational design" or
"biomimicry," Prof. Gurevitz is trying to
develop painkillers that mimic the venom's
bioactive 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.
No more morphine addicts
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 which aspirin
could never palliate. 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. 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
University's Department of Plant Sciences is
investigating new ways for developing a novel
painkiller based on natural compounds found
in the venom of scorpions. These compounds
have gone through millions of years of
evolution and some show high efficacy and
specificity for certain components of the body
with no side effects, he says.
Peptide toxins found in scor...pion venom
interact with sodium channels in nervous and
muscular systems -- and some of these
sodium channels communicate pain, says
Prof. Gurevitz. "The mammalian body has
nine different sodium channels of which only
a certain subtype delivers pain to our 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 we figure this out, we may be able to
slightly modify such toxins, making them
more potent and specific for certain pain
mediating sodium channels," Prof. Gurevitz
continues. With this information, engineering
of chemical derivatives that mimic the
scorpion toxins would provide novel pain
killers of high specificity that have no side
effects.
An ancient Chinese secret?
In his research, Prof. Gurevitz is
concentrating on the Israeli yellow scorpion,
one of the most potent scorpions in the
world. Its venom contains more than 300
peptides of which only a minor 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 the use of scorpion venom to treat
some body disorders seems counter-intuitive,
the Chinese have recognized its effectiveness
hundreds of years ago. "The Chinese, major
practitioners of what we call 'alternative
medicine,' use scorpion venom, believing it to
have powerful analgesic properties," Prof.
Gurevitz says. Some studies have also
shown that scorpion venom can 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."
Using an approach called "rational design" or
"biomimicry," Prof. Gurevitz is trying to
develop painkillers that mimic the venom's
bioactive 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.
No more morphine addicts
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 which aspirin
could never palliate. 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. 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
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