THE AUSTRALIAN (Sydney, Australia) 16 January 10 Healing in a serpent's tooth: snake venom (Derek Parker)
Snakes aren't usually considered a national asset, especially those dangerous enough to kill. But that could change if the push to utilise snake venom for a range of medical purposes proves as effective as experts predict.
The process recently took an important step forward with an Australian company called Venomics on-licensing the rights to commercialise two product candidates, textilinin and HaempatchTM, both derived from Australian snake venom. Venomics is a spin-off from QRxPharma, established in 2002 to commercialise therapeutics research from the University of Queensland.
The products were developed by UQ researchers John de Jersey and Martin Lavin, along with Paul Masci who's studied Australian snake venoms for more than 20 years in search of drug candidates.
Textilinin has the potential to reduce blood loss in surgery by helping to maintain blood clots in place once they've formed. So far, it compares favourably with other so-called antifibrinolytic drugs, showing reduced blood loss and less potential for side effects.
HaempatchTM clots blood effectively and is being developed as a topical clotting agent to stop blood flow from surgical or trauma wounds. It has shown promising results in pre-clinical testing, including the ability to form clots faster and with less blood loss than comparable drugs now in use.
Both products are moving through testing, with clinical trials likely in two or three years.
Venomics was created as part of a joint venture with Liaoning Nuokang Medicines, a leading biopharmaceutical company based in Shenyang, China. Nuokang's flagship product, Baquting, is used in China for treatment of bleeding in surgery. It contains an enzyme obtained from the venom of a South American snake, the common lancehead.
Under the joint venture, the Chinese rights for both products have been licensed to a Nuokang subsidiary. Venomics has the right to use developmental data generated by Nuokang to seek licensing and development deals in the rest of the world.
"There is a sense of escalating interest in the potential of venom-derived pharmaceutical products," says Stephen Earl, manager of research and development for Venomics. "QRxPharma and now Venomics have partnered with researchers from UQ to comprehensively screen Australian snake venoms for further drug candidates. This project began in 2004 and we have already screened the venom of 20 Australian snakes, so we are building a database," Earl says of the work, funded by two Australian Research Council Linkage grants totalling more than $2.7 million.
Earl, a toxinologist, has long been fascinated by snake venom, as well as the potential for development of new drugs. "Whether a snake is defending itself or hunting for food, the purpose of venom is to alter biological functions," he says. "That is the basic purpose of medicine, too. As a researcher, you observe the action of the venom and look for ways to apply it in a therapeutic context.".
Worldwide, there are about 650 species of venomous snakes. Ten of the most deadly live in Australia, including tiger snakes, brown snakes, death adders and taipans. Significantly, Australia's snakes have evolved so their venom is targeted at mammals, making them a rich source of venom components compared with the snakes of other countries.
"Textilinin and HaempatchTM are both derived from venom from the Australian common brown snake," Earl says. "And there is another product coming through the process, also based on common brown snake venom, which has a lot of potential."
Called CoVase, it shows promise as a systemic clotting agent, useful in the treatment of internal bleeding, trauma and haemorrhagic stroke. Unlike many other clotting agents, which can only be delivered as a topical treatment, Earl claims it could be delivered intravenously, which expands the therapeutic options greatly.
Several drugs based on venom components are already in clinical use and others are in clinical trials. One recent success story is the development of ACE inhibitors, a class of blood pressure medication originally derived from the venom of a Brazilian snake.
There's also a range of diagnostic tests that use snake venom. The common brown snake venom is used in a diagnostic test for lupus anticoagulants, a condition that can lead to miscarriage, stroke or other cardiovascular conditions.
A problem for researchers looking for possible medical uses is the complex makeup of venoms. To find the component of interest, the venom must be separated by the different molecular weight of its constituent proteins, a process known as column fractionating. Once the target agent is found, it can be manufactured by culturing in a bacterial medium.
Aside from Venomics and UQ, a key research agency is the Venoms Research Group at the school of pharmacy and medical sciences in the University of South Australia. "Venom research is currently moving in quite a few directions," Michael Venning, head of the VRG, says. "We are looking at the use of death adder venom as a means of controlling high blood pressure, for example. All Australian snakes are from the elapid class, so their venom is rich in neurotoxins . . . But there are also antibacterial properties with the potential for the targeting of specific infections."
Venning, a pharmacologist, says one of the most interesting avenues of research is into the effect of a compound in death adder venom that disrupts endothelial cells, lining the inner surface of blood vessels. Called the antiangiogenic effect, it could be useful in the treatment of cancer, preventing the growth of tumours by cutting off the blood supply.
Virtually all the venoms used in Australian medical research originate from Venom Supplies in SA's Barossa Valley. "From the perspective of drug potential, Australia's venomous snakes are like slithering pharmacies," Peter Mirtschin, managing director of Venom Supplies, says. "We have only scratched the surface."
Mirtschin is an adjunct research fellow of the University of South Australia and was pivotal in the establishment of the VRG in the mid-1990s.
His farm has more than 500 snakes, including more taipans than any other venom farm in the world. Venom Supplies has a long-term contract to supply taipan venom to a US pharmaceutical company. An associated company, Venom Science, will soon begin manufacture of a diagnostic kit for the horse-racing industry. Based on cobra venom antibodies, the kit determines whether cobra venom -- which like many venoms has potent analgesic properties -- has been used illegally to treat racehorses.
Mirtschin has discovered that taipan venom has a property that helps break down its prey for digestion. He suspects it could lead to treatments for people who cannot make digestive enzymes or whose pancreas is failing.
"There is so much to explore," Mirtschin says. "Not only are the venoms of every snake species different, there are also variations within each species."
But he is worried. He says successive environmental audits indicate authorities aren't protecting native species. The tiger snake, for instance, was once abundant but is now hard to find.
"If we are to halt the loss of these resources, drastic changes must be made in thinking."
He adds: "The clock is ticking if we are going to take advantage of this resource before it disappears."
Healing in a serpent's tooth

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• AUS Press: Healing in a serpent's tooth - W von Papineäu, Sat Jan 16 16:54:54 2010