SYDNEY: A little studied group of venomous lizards harbour unknown toxin types which may soon be used to treat patients with high blood pressure, according to an international team of researchers.
During the four-year, multidisciplinary study, researchers from across the world, including Belgium, the Netherlands, Ireland, Switzerland, Israel and the U.S., examined a group of lizards known as anguimorphs to discover these venoms.
“Back in 2006 we showed this ancient presence of venom,” said Bryan Fry from the University of Melbourne. “However we looked at only a small taxonomically limited sample of this 130 million year old lizard group.”
Venom more widespread than thought
Until 2006, it was thought that venomous lizards were rare, restricted to the likes of the gila monster, bearded lizard and komodo dragon.
By examining 23 species of anguimorphs, which includes monitors, alligators and legless lizards, to span the full diversity of this group, it was found that the presence of venom was far more widespread, the researchers reported in the journal Molecular and Cellular Proteomics.
“We sequenced new forms from nine known toxin types, but also discovered five entirely new toxin types,” said Fry. “We showed a great diversity of toxins in anguimorph venoms. The drug design potential of these novel venoms is highlighted by the fact that three of these new toxins act to lower blood pressure.”
Harnessing a lethal weapon
Lizards use venom to slow down or immobilise a prey item by lowering its blood pressure. In extreme cases, the prey can even faint or experience full hypotensive shock.
Some lizards, such as the komodo dragon, still inflict the killing blows with their teeth, the venom ensuring continued blood flow and lowered blood pressure in their prey after the large, deep wounds have been made.
Meanwhile, lizards from the Heloderma genus – such as gila monster and bearded lizards – use the immobilising properties of venom as their primary hunting weapon, their delicate teeth specialised in delivering venom rather than severe wounds.
Pharmaceutical potential of new toxins
The toxins contain peptides – a naturally occurring compound composed of two or more amino acids – which work by restricting the production of the ‘Angiotensin-converting enzyme (ACE)’. ACE is responsible for contraction of the muscles surrounding blood vessels, which builds pressure.
However, Fry still needs to figure out how to convert the newly found peptides into ACE-inhibiting drugs for the treatment of heart disease.
If successful, these drugs will join the type 2 Diabetes treatment called Byetta, as being commercially sold pharmaceuticals developed from lizard toxins. Made using a synthetic version of the exendin-4 toxin from the gila monster, Byetta has shown commercial success for the past five years.
Snakes and lizards share common ancestor
Coupled with the discovery of new venom types, the results of this study provided valuable insight into the evolution of reptile venom delivery systems.
It had previously been assumed that these delivery systems had evolved independently in snakes and lizards, however it has now been found that all snake and lizard species with oral glands for toxin secretion share the same ancestor, indicating a single origin of these venom systems.
While snakes evolved a sophisticated delivery system involving a high-pressure injection mechanism facilitated by their fangs, over the 130 million year lifespan of the Anguimorpha group, these lizards developed a less sophisticated system involving venom secretions in the saliva.
“The discovery of a new source of venoms in lizards previously thought to be non-venomous is exciting given our growing recognition that venom peptides can be developed into drugs,” said Richard Lewis of the University of Queensland Institute for Molecular Bioscience.
“Particularly exciting is the identification of novel inhibitors of blood pressure that have the potential to be leads to, or generate new ideas for, the development of new anti-hypertensives.”