Sea snail venom could become the gold standard for the relief of nerve-related pain following the development of a pill that is 100 times as potent as leading treatments.
Current treatments for neuropathic pain include morphine, which is highly addictive, and gabapentin, which both act on nerve receptors. Sea snail venom had been suggested as a good alternative because it consists of a cocktail of peptides, known as conotoxins. These act to immobilise prey by blocking nerve-cell conduction, but in mammals the peptides are an effective analgesic.
The only conotoxin-derived drug approved for human use is ziconotide. Unfortunately, the drug is susceptible to breakdown by enzymes in the saliva and gut, so it is administered by a pump surgically inserted into the abdominal wall, making it an invasive and expensive treatment.
To solve this problem, David Craik and his team at the University of Queensland in Australia have developed the first "orally active" conotoxin drug.
They started with a synthetic version of conotoxin. Since the enzymes that break down the drug usually act at the ends of the conotoxin molecule, the team used a chain of amino acids to join up these ends to form a circular structure. They found this version to be resistant to enzymes in the body.
Craik's team tested the conotoxin in rats with neuropathic pain. They found that a single oral dose significantly reduced pain using a standard test – how much pressure the rat could withstand before withdrawing its paw. Compared with gabapentin, conotoxin was judged to be 100 times more potent.
Because the conotoxin is so powerful, only very small doses are needed, reducing the risk of side effects, says Craik. His team has applied for approval from the US Food and Drug Administration for a trial in humans.