Scientists use a synthesized version of poison from a scorpion to treat recurring brain tumors in cancer patients.

Scorpion venom is responsible for 10 times as many deaths per year as snake venom. But the deadly poison could also become an effective new cancer treatment.

Scientists have used synthetic venom, called TM-601, to deliver small doses of radioactive iodine to brain tumor cells in human patients. Unlike other forms of radiation treatment for cancer, the small protein targets brain tumor cells without harming neighboring healthy tissue or other organs.

“The idea of targeted radiation is that by sticking the radiation on something that sits on the tumor cells preferentially, you’ll localize that radiation to the vicinity of the tumor cells,” said Adam Mamelak, a neurosurgeon of Cedars-Sinai Medical Center in Los Angeles and lead author of a study puslished in the August issue of Journal of Clinical Oncology. “So, you’re getting a selective killing with the radiation.”

TM-601, which is chemically identical to natural scorpion venom, works by binding to a specific type of receptor that appears on the surface of malignant tumor cells. Anything that is “piggybacked” on the protein—in this case, radioactive iodine—is delivered locally to the cells.

In current forms of radiation treatment, doctors attack tumor cells with an external source of X-rays. The method is relatively non-specific and can damage normal cells as well as cancerous ones.

Eighteen patients participated in the study, all of whom had recurrent malignant brain tumors. Within a month of undergoing tumor-removal surgery, the subjects were injected with TM-601, carrying a single dose of radioactive iodine, through a catheter inserted into the cavity where the tumor had been removed. Researchers found that the compounds were not only localized to the tumor cells, but they were also nontoxic.

“Everybody in the study did at least as well as the average for this patient population, and we had a few patients that had durable responses,” Mamelak said, “Two patients lived two and a half to three years from the time of the injection, which is pretty remarkable, because the dose that we gave is so far below any dose that should really have a therapy effect.”

Researchers have attempted to target malignant brain tumors with antibodies before, but according to Mamelak, these antibodies are too large to get into the brain. (An antibody is typically hundreds of amino acids long, while TM-601 is composed of only about 30 amino acids.) What’s more, antibodies aren’t as selective as TM-601 in their binding to tumors.

Yancey Gillespie, a professor of neurosurgery at the University of Alabama at Birmingham, who has studied TM-601 in mice, said that since the protein is so small, it diffuses through the blood-brain barrier to bind with tumor cells. He added that due to malignant brain tumors’ tendency to recur within 2 cm of their initial location, localized therapy using TM-601 would be especially useful.

“It’s a clever approach, from the standpoint of how the molecule actually seems to function,” Gillespie said.

TM-601 is now in phase II of clinical trials, where researchers are testing it in higher and more frequent doses. In the future, they hope to determine whether it is useful for targeting other types of metastatic tumors—like those that occur in lymphoma, melanoma and lung cancer—and whether compounds other than iodine would be more effective. Because TM-601 is so small, doctors may also be able to someday administer it intravenously. Mamelak says many of these questions will be answered within three to five years.

“Really,” he said, “we’re at the tip of the iceberg right now.”

Originally published August 8, 2006


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