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Drugs with biteMonash University scientists are testing the toxins in sea snake venom in the hope they could become a novel source of drugs. PENNY FANNIN reports.
The venoms are devastatingly effective due to toxins they contain that cripple the prey's nervous system. Now Monash University scientists are investigating whether these toxins might prove useful in the global search for new drugs. For several years, a worldwide search for new lead compounds for use in drug development has been under way, with many scientists focusing their attention on forests, searching for possible compounds in tree bark and fungi. But Dr Wayne Hodgson, a senior lecturer in the university's Department of Pharmacology and head of the Monash Venom Group, believes it is Australia's venomous creatures that could prove to be a valuable source of potential medicines. In the past, many toxins have been adapted or have served as lead structures for therapeutic, diagnostic and insecticidal agents. Dr Hodgson's group is interested in whether the toxins found in the venom of Australian animals might be used in the same way. "In Australia we have the world's most potent collection of venomous creatures, but the research focus has been on making sure we have anti-venoms so that people don't die," Dr Hodgson says. "There are a number of toxins found in snake venoms that have evolved to target vital processes in the body, and they appear to have a lot more selectivity than many drugs that have been developed." Dr Hodgson, Dr Richard Loiacono, Mr Janith Wickramaratna, Ms Nav Chetty and Ms Amanda Du from the Department of Pharmacology are concentrating their efforts on finding toxins that might help treat conditions including brain diseases. They are isolating toxins from the venom of sea snakes and death adders to see if they can target particular receptors in the brain that appear to be involved in learning and memory, as well as protecting the brain. The venoms are collected and 'screened' against different animal tissues - usually against a muscle removed from the back of a chicken's neck - so that the neurotoxins - toxins that impair the nervous system - can be identified. Chicken neck muscles are used because they are physiologically similar to the human diaphragm, and one of the major problems in humans who have been injected with venom is respiratory paralysis. Generally, between three and six neurotoxins are isolated from the venom of each snake species. Each neurotoxin is then tested. Under normal circumstances, when the chicken tissue is electrically stimulated, the nerves in the tissue cause it to contract. But when the tissue has been exposed to neurotoxins (which interfere with the nerve pathways), the contraction process is inhibited. "This inhibition also occurs when humans have received a dose of venom, except that it stops their respiratory muscle from contracting and makes breathing difficult," Dr Hodgson says. "The neurotoxins have an effect on the chicken muscle and the human diaphragm because they bind to what is known as a nicotinic receptor - similar receptors are also found in the human brain," he says. "We think neurotoxins might be useful for working out what is happening in the brains of people with memory disorders such as Alzheimer's because, in these patients, the nicotinic receptors in the brain don't work properly." Preliminary studies by the venom group suggest that the neurotoxins found in venoms are very potent at targeting nicotinic receptors in the brain. "From our work so far it seems the death adders have the most potent toxins of all the terrestrial snakes, but sea snakes are even more potent than the death adders." By targeting the nicotinic receptors in the brain with the neurotoxins, Dr Hodgson and colleagues in the depart-ments of Pharmacology and Biochemistry are investigating diseases such as Alzheimer's, the role that these receptors may play in the progression of the disease and how the neurotoxins can pave the way for treatments to be developed. The Monash Venom Group is also pursuing another facet of venom research - developing alternative treatments to anti-venoms. Dr Hodgson says there is a particular need for alternative treatments in many Southeast Asian and Pacific countries such as Papua New Guinea, Indonesia and Vietnam where the rates of snakebite are high but supplies of anti-venom are low. This is partly due to the prohibitive cost of the anti-venoms and partly due to a lack of suitable storage facilities - anti-venoms need to be kept refrigerated. "In Asia between 35,000 and 50,000 people die from snake bite each year, so there is a real need for alternative treatments," Dr Hodgson says. "It's unlikely that people are going to develop new anti-venoms because it's not a lucrative market, so we have to find ways of treating people with existing drugs." 
Underwater resource: Dr Wayne Hodgson believes Australia's venomous sea snakes could be a valuable source of potential medicines. Action box |
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In the tropical waters that envelop northern Australia and flow toward Indonesia, sea snakes can be found in their thousands. Over millions of years of evolution, these reptiles have become increasingly skilled at using venoms to immobilise their prey.