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Scorpion Venom Tested Against Brain Cancer

In preliminary trial, protein seemed to prolong patients' lives

FRIDAY, July 28, 2006 (HealthDay News) -- A synthetic version of a protein found in scorpion venom has passed its first test in a treatment for one of the deadliest forms of cancer and is headed toward trials against other tumors.

The protein, designated TM-601, not only carried radioactive iodine directly to the brain tumor called glioma, but also appeared to have anticancer activity of its own, said Dr. Adam N. Mamelak, a neurosurgeon at the Cedars-Sinai Medical Center's neurosurgical institute in Los Angeles. He was lead author of a report on the therapy in the August issue of the Journal of Clinical Oncology.

TM-601 has an unusual ability to pass through the blood-brain barrier that keeps most chemicals from reaching brain tissue. It also binds to glioma cells, which are vulnerable to the radioactive iodine carried by the protein, Mamelak said.

The treatment was tried in 18 patients whose glioma recurred after surgery, which usually means death within months.

"Two of the 18 patients had long survival, about three years post-treatment," Mamelak said. "Six of 18 survived significantly longer that the typical patient population."

An estimated 17,000 Americans are diagnosed with gliomas each year. These tumors are extremely aggressive and deadly; only 8 percent of patients survive two years and 3 percent survive five years after diagnosis. And when surgery is performed to remove a glioma, some malignant cells invariably remain behind and proliferate, the researchers said.

TM-601 was developed in the laboratory of Harold Sontheimer, a neurobiologist who heads the Civitan Research Center of the University of Alabama at Birmingham. It acts by blocking chloride channels in cells, Sontheimer explained, the same action that helps paralyze cockroaches, the prey of the Giant Yellow Israeli scorpion. In humans, that action prevents tumor cells from invading surrounding tissue, he said.

TM-601 has been licensed to a Birmingham, Ala., company, TransMolecular Inc., which helped finance the study. It was a Phase 1 trial, the first step in the long process of gaining U.S. Food and Drug Administration approval for medical use.

One major purpose of a Phase 1 trial is to test safety, and "we were very pleased that there was a very good safety profile," said Michael Egan, president and chief executive officer of TransMolecular.

"There was essentially no toxicity," added Mamelak. "Whatever didn't bind to the tumor didn't go anywhere. It was washed out of the body."

A Phase 2 trial that will enroll 54 glioma patients at 20 medical centers around the country has begun recruiting participants, Egan said. One purpose of the trial will be to determine the best dosage schedule, he said. Results are expected some time next year.

Plans are also being made for trials of TM-601 against other forms of cancer, Egan said. The targets would be "multiple solid tumor types, any solid tumor," such as breast cancer or colon cancer, he said.

There are indications that TM-601 is more than just a radiation carrier, Mamelak said. "The idea is that it may be synergistic and potentiate the effects of other therapies," he said.

The nasty side of venom was the subject of another report, this one by researchers at Stanford University School of Medicine. It has been thought that the body's immune system worsens the nausea, numbness, convulsions and other effects of venom. But mouse studies of four venoms -- three from snakes and one from a bee -- showed the immune system did fight the ill effects of those venoms, reducing the symptoms, said the report in the July 28 issue of Science.

More information

To learn more about brain tumors, visit the U.S. National Library of Medicine.

SOURCES: Adam N. Mamelak, M.D., neurosurgeon, Cedars-Sinai Medical Center, Los Angeles; Harold Sontheimer, Ph.D., director, University of Alabama at Birmingham Civitan Research Center; Michael Egan, president, TransMolecular Inc., Birmingham, Ala.; August 2006, Journal of Clinical Oncology; July 28, 2006, Science
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