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Sea Snail Venom Yields Powerful New Painkiller

By Alisa Zapp Machalek

People whose pain is unresponsive even to morphine may now find relief from an unlikely source — the venom of a poisonous sea snail. A new drug derived from this venom became available to patients just recently. It is the culmination of decades of basic research supported by the National Institute of General Medical Sciences.

The new medicine, called Prialt, or ziconotide, has its roots in a boy's curiosity about
Dr. Baldomero Olivera
the deadly poisons inside the beautiful shells he collected in his native Philippines. Now a professor of biology at the University of Utah, Dr. Baldomero Olivera analyzes the highly toxic venoms of these cone snails. His research is backed by 25 years of NIGMS funding.

Prialt is 1,000 times more powerful than morphine, but, unlike morphine, it is not believed to be addictive. The FDA approved its use for chronic, intractable pain such as that suffered by people with cancer, AIDS or certain neurological disorders. It is delivered directly into fluid surrounding the spinal cord by external or implanted pumps.

The new drug is a synthetic compound identical to a toxin in the venom of the Conus magus snail. This is remarkable in itself, because natural compounds are almost always chemically modified to make them work better as drugs. In this case, nature perfected the compound on its own.

Also noteworthy is that the toxin was discovered by a teenager named J. Michael McIntosh, who, just days after graduating from high school, began assisting Olivera with his research. Now, 25 years and an M.D. degree later, McIntosh is a research psychiatrist at the University of Utah. He still collaborates with Olivera on the cone snail research.

Prialt, which is marketed by Elan Corp. of Dublin, Ireland, may be just the first of many new medicines derived from cone snail venom. There are about 500 different types of cone snails, and each one typically produces about 100 different toxins in its venom. According to Olivera's research, the toxins affect the nervous system in different ways — some instantly shock the snail's prey, as does the sting of an electric eel, scorpion or sea anemone. Others cause paralysis, like the venoms of cobras and Japanese puffer fish.

These are shells of Conus magus, or magician's cone snail, from which the new drug Prialt is derived. Native to coral reefs in the Pacific Ocean, the 2-inch-long snail uses its venom to hunt fish. Some of the larger cone snails contain enough venom to kill a human with a single sting.

Olivera's investigations further revealed that each toxin targets a certain type of molecule, usually a "channel" protein that helps pass messages in the nervous system. For example, the Prialt molecule blocks calcium channels in specific nerve cells, preventing certain pain signals from reaching the brain. The toxins are so accurate at pinpointing their targets that researchers now use them to identify and study specific brain proteins.

The extreme specificity of the compounds — a characteristic highly prized in drug molecules — has not escaped the notice of pharmaceutical companies. Already, they are testing the potential of dozens of cone snail toxins to treat epilepsy, cardiovascular disease and other disorders.

Olivera continues to study and synthesize toxins produced by cone snails. He believes — and his research supports — that the snails are a treasure trove of novel chemical compounds with the potential to be useful in the clinic or laboratory. Eventually, Olivera hopes to harness the molecules to treat Alzheimer's disease, Parkinson's disease, schizophrenia and depression.

For more information about Olivera and his work on cone snail toxins, visit http://www.nigms.nih.gov/news/findings/sept02/snails.html.
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