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For its prey, a carnivorous cone snail is a nightmare: this tiny mollusk packs enough venom in one sting to kill. And yet, that same venom has pharmacological possibilities—relief for insomniacs.
Past research into cone snail venom has already revealed the toxin as potential pain medication, but work by two Indian scientists, Jayaseelan B. Franklin and R. P. Rajesh, has unveiled new properties that might help soothe the sleepless. The team, looking for more therapeutic peptides from the marine gastropod, focused on the rarely studied cobweb cone snail (Conus araneosus)—a small snail endemic to the Gulf of Mannar, between India and Sri Lanka.
Every cone snail’s venom is packed with hundreds of peptides. Franklin and Rajesh identified 14 peptides in the cobweb cone’s venom and zeroed in on five for further study. It took more than six months to purify and isolate the peptides, but when they were finally administered to lab mice the peptides had a fast and surprising effect: within two to four minutes the rodents fell asleep and stayed asleep for about two hours. When the dosage was increased two-and-a-half times, the mice took longer to fall asleep (about 10 minutes), but slept for five hours. “The peptide-treated mice attained complete normal active behavior only after nine or ten hours,” explains Franklin.
The sleep-inducing properties of the cobweb cone snail’s toxin is the first such discovery and the findings open up the prospect of studying the snail’s venom for diagnostic or therapeutic use in humans—particularly in treating sleep disorders such as insomnia and sleep apnea. “Finding the mechanism that caused this effect on the mice will open up future applications including drug development,” says Franklin.
Cone snails prey on fish, mollusks, or worms. Moving literally at a snail’s pace, they have a short opportunity to hunt so they pack lethal compounds in their venom called conotoxins to stun their victim.
Scientist Mande Holford, an expert in venomous marine organisms, says, “Cone snail venom is a cluster bomb of highly specialized compounds.” A venom-filled sting from the cone snail’s harpoon-like tooth impedes the normal cellular function of prey, paralyzing the animal and rendering it helpless as its predator begins to dine.
For the last few decades, cone snail venom has emerged as one of the most popular naturally derived substances in biomedical research. More than 100 conotoxins have been studied and many are in clinical and preclinical trials for treating cancer pain, post-operative pain, hypertension, epilepsy, Alzheimer’s disease, and Parkinson’s disease. In 2004, Prialt, a painkiller more powerful than morphine, became the first conotoxin peptide approved for public use.
New properties of cone snail venom continue to be found. Earlier this year, scientists from the University of Utah discovered cone snails that use insulin to induce low blood sugar in their prey, a tactic that immobilizes the victim.
“There are at least 800 species of cone snails and venom from each one has 1,000 peptides. We’ve discovered what just one of these does,” says Franklin. “We have a lot more work to do.”