The Filipino cone snail normally spends its days sliding across the sea floor, snaring fish with its venomous, harpoon-like tooth. But if it washes ashore, steer clear. Beachcombers who pick it up or step on it receive a deadly dose of poison. Islanders call it the cigarette snail: the sting leaves you time for one last smoke.
Now, Stanford researchers have shown that an ingredient in the snail toxin can take the sting out of chronic pain. The ingredient, a protein fragment, appears to be a powerful painkiller “in a class of its own,” reports Michael Leong, an assistant professor of anesthesia. “It has great potential for patients who can’t get relief from other drugs.”
Biomedical scientists became intrigued by the killer snail, Conus magus, in the early 1980s. Upon analyzing the toxin, they found it to be a protein that inhibits the central nervous system. A decade later, researchers at Neurex Inc. (now ´Elan Pharmaceuticals) chopped the protein into fragments and administered these to rats, looking for possible medical effects.
In the new study, funded by ´Elan, Leong and his colleagues tested a fragment called ziconotide in people suffering chronic pain from conditions such as AIDS and cancer. “Over half of those treated showed a marked improvement,” he says of the drug, currently under fda review. “Fifty percent may not seem like much, but we’re talking about people for whom nothing worked before.”
The unusual painkiller is a calcium-channel blocker that works mainly on cells of the central nervous system. These nerve cells use calcium molecules to signal neighboring cells, spreading the pain response. By blocking calcium release, ziconotide dampens that response. Preliminary studies by Leong and his colleagues at the Stanford Pain Management Center suggest that the drug also has a protective effect, desensitizing nerve cells in advance of any signal so that they are less likely to respond.
In contrast, conventional pain drugs such as morphine do not target pain at a molecular level. This difference could be a tremendous asset, Leong speculates, because the two drugs might be given simultaneously and work synergistically on distinct types of pain. Moreover, since ziconotide is not an opiate, it is not addictive and has no narcotic side effects. The Stanford team found that patients receiving it did not build up a tolerance, so there was no need to increase doses over time.
There’s even good news for the snail. Knowing the exact composition of the protein, scientists can now synthesize it—leaving Conus magus to slither back into obscurity.
