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| Cone snail--Courtesy of Bruce Livett and David Paul |
A tiny protein found in cone snail venom could provide the foundation for a new class of drugs to treat chronic nerve pain, according to scientists.
Investigators from the University of Queensland say they've produced at least 5 new experimental substances derived from cone snails, predatory sea snails that use venom to paralyze their prey. They say the substances could be used to develop safe and effective oral medications to treat chronic nerve pain and may be stronger than morphine with fewer side effects and lower risk of abuse. The research was presented this week at a meeting of the American Chemical Society.
The venom of these animals contains hundreds of peptides called conotoxins, some of which seem to have painkilling effects in humans. So far, ziconotide is the only FDA-approved conotoxin-derived medication, but it must be administered as an infusion into the lower part of the spinal cord. The team is working to develop a less invasive conotoxin-based drug that could be taken orally.
In laboratory rats, scientists tested a single, small oral dose of a prototype drug based on a looped conotoxin--modified peptides that form a circular chain of amino acids. In previous research, the team found that these looped conotoxins are extremely stable and resistant to enzymes in the body. The looped conotoxin drug appeared to significantly reduce pain in the rats. The researchers estimate that this prototype drug was about 100 times more potent than morphine or gabapentin, commonly prescribed drugs for chronic nerve pain.
Conotoxins carry less risk of addiction than opiate drugs like morphine because they act on different receptors in the brain.
"We don't know about side effects yet, as it hasn't been tested in humans. But we think it would be safe," said study lead author David Craik, laboratory head of the chemistry and structural biology division at the University of Queensland. "It acts by a completely different mechanism than morphine so we think it has a minimal possibility of producing the side effects of that medication. That is one of the big advantages of this drug."
Craik and his colleagues are currently evaluating 5 new substances based on the looped conotoxin prototype drug they've developed and hope to test these experimental drugs in humans soon.
Chronic pain, or neuropathic pain, is often triggered by diabetes, multiple sclerosis and other diseases and can last for months, years or decades.
- read the press release
- get the meeting abstract