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New painkiller was born in Utah


Undergrad discovered natural form in venomous snails in 1979

The natural form of Prialt – a new drug for severe pain approved this week by the U.S. Food and Drug Administration – was discovered at the University of Utah in 1979 by an incoming freshman studying toxins produced by cone snails.

The student, J. Michael McIntosh, worked in the laboratory of University of Utah biologist Baldomero "Toto" Olivera, the summer before his freshman year as the result of a scholarship interview. Now, 25 years later, Olivera is a distinguished professor of biology who still studies cone snails and how substances in their venom may be developed into drugs, and McIntosh is a professor of psychiatry and research professor of biology at the university.

McIntosh says his experience as an 18-year-old working in Olivera’s laboratory shows "the university provides a very unusual opportunity for undergraduate students to participate in cutting-edge research that can make a real difference."

Olivera says McIntosh first isolated and characterized the painkiller in the venom of the fish-hunting cone snail Conus magus, or magician’s cone, which is about 1.5 inches long and thus too small to kill people it stings, as do some larger cone snails.

McIntosh discovered a component or "factor" in the venom affected the nervous system. He purified it and determined its chemical structure. Later, University of Utah biologist Doju Yoshikami determined the factor blocked the transmission of nerve signals through certain connections or synapses between nerve cells.

Olivera and Yoshikami developed the factor – named omega-MVIIA, or omega conotoxin M seven A – for use in basic research in neuroscience. "It blocks communication between nerve cells," allowing researchers to learn what nerve circuits do normally by seeing what goes wrong when the connections are blocked, Olivera says.

The university didn’t patent omega-MVIIA because the substance "didn’t have a definitive therapeutic use" at the time, he adds. "As with many basic science discoveries, the clinical importance of the discovery wasn’t appreciated at the time," McIntosh says.

Olivera and Yoshikami collaborated in basic research on omega-MVIIA with George Miljanich, who worked at the University of Southern California and later moved to Neurex Corp., where Miljanich explored the substance’s therapeutic potential.

Neurex ultimately was acquired by Elan Corp., based in Dublin, Ireland. On Dec. 28, Elan got FDA approval to sell Prialt for chronic, intractable pain suffered by people with cancer, AIDS, injury, failed back surgery or certain nervous system disorders.

The drug is expected to be available in the United States in late January 2005. It is injected into fluid surrounding the spinal cord by external or implanted pumps. "The commercial product, Prialt, is chemically identical to omega-MVIIA, except that it is made synthetically instead of by snails," Olivera says.

McIntosh now directs research in the Department of Psychiatry at the University of Utah Health Sciences Center, and treats adolescents and adults who have depression, anxiety, bipolar disorder (manic-depression) and obsessive-compulsive disorder.

Baldomero | EurekAlert!
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