Marine Snail Venom Tested for Relief of Diabetes Pain

MELBOURNE, Australia, June 13, 2005 (ENS) - The venom of a marine cone snail found in tropical waters off the coast of Australia shows promise in relieving the most difficult form of pain to treat, new research by university and corporate scientists reveals.

The venom has shown potential for treating pain generated inside the body, associated with damage to nerves. Called neuropathic pain, it is associated with many conditions, including surgery, cancer, AIDS, diabetes, multiple sclerosis, shingles and sciatica.

Scientists say this type of pain is different from pain which comes from the outside the body, if someone is burned, for instance, or hit.

All cone snails produce venom which they use to paralyze prey before killing and eating them. Bruce Livett, an associate professor with the University of Melbourne and the recently launched Bio21 Institute, has discovered that cone snails inject a pain reducing substance into their prey as they inject the venom, and that is what interests researchers.

Livett says, “It appears that cone snails have adopted the general strategy of including a pain reducing component among the more lethal components of its venom.”

Livett

Bruce Livett says neuropathic pain typically responds poorly to conventional painkillers such as morphine or aspirin. (Photo courtesy U. Melbourne)
The venom of some cone snails is toxic to humans - as many as 30 people are known to have died from cone snail venom, but not all cone snail venoms are the same.

There are over 500 species of cone snail, each with a different cocktail of venom peptides and up to 200 components in each venom, says Livett, whose team at the university's Department of Biochemistry and Molecular Biology discovered the phenomenon.

A cone snail has a cone shaped shell, a fleshy foot, a head, and tentacles. Cone snails live in the Indian and Pacific Oceans, the Caribbean and Red Seas, and along the coast of Florida. They are not aggressive, and the sting usually occurs when divers in deep reef waters handle the snails.

Livett is working with the Melbourne based company Metabolic Pharmaceuticals Ltd, which recently announced successful results in preclinical trials of the toxin, called ACV1, derived from the venom of Conus victoriae.

The company will begin clinical trials in humans this month, first to test the safety of the toxin in normal males, and later its effectiveness in treating the neuropathic pain associated with diabetes.

“ACV1 has been shown to be effective in treating pain in several experimental animal models of human pain syndromes, including post-surgical and neuropathic pain,” Livett says. “In addition, it has the unique property that it appears to accelerate the rate of recovery from a nerve injury.”

cone snail

A coneshell, Conus textile, in the Livett laboratory tank (Photo courtesy U. Melbourne)
ACV1 is not the only therapeutic compound that cone snail venom has to offer. Instead, the venom is a cocktail of thousands of biologically active compounds, yet only a few hundred have been identified.

Associate Professor Ken Gayler, also with the university's Department of Biochemistry and Molecular Biology, says the team, by using genes as the starting point, has been able to minimize the number of cone snails required to develop new tools and therapies for medical research and therefore minimize the environmental impact of the research.

“With a single cone snail we can create and store large libraries of conotoxin genes,” Gayler said.

It was using this genetic mining technique that ACV1 was discovered – its peptide sequence was predicted solely from the DNA sequence.

The peptide was then chemically synthesized in large quantities suitable for biological testing. This same approach is now being used by Metabolic Pharmaceuticals to synthesize gram amounts of ACV1 needed for the planned human clinical trials for diabetic neuropathy.

“With an increasing age demographic in our society the need for more effective pain suppressing compounds is a priority. But the common use of opiates to treat these painful conditions is not always appropriate," Livett says.

ACV1 may fill this need. Other cone snails, marine sponges or soft corals may yield substances that will make it easier to quit smoking tobacco.

Livett says studies are under way in collaboration with organic chemists, protein/peptide chemists and molecular modellers, to investigate natural products from these marine creatures as sources of nicotinic receptor blockers.