Scorpion Venom May Help Treat Brain Cancer

Scientists hope a chemical from a scorpion's sting will "paint" brain tumors.

ByDan Childs<br>abc News Medical Unit
August 08, 2008, 3:54 PM

Aug. 11, 2008&#151; -- The sting of the Giant Yellow Israeli Scorpion packs a painful punch. Its venom contains a potent cocktail of neurotoxins that places an animal or human victim in excruciating agony.

It's not the first place most would think to look for a weapon against cancer. But doctors and researchers report that a particular component within this dangerous mix may be able to seek out brain tumor cells. And one researcher, as reported by ABC affiliate KOMO-TV in Seattle, hope that doctors will one day be able to use this property to "paint" tumors for a surgeons to see.

"Right now it is difficult for a surgeon to be able to distinguish a brain tumor from the normal brain tissue around it," says Dr. James Olson of the Fred Hutchinson Cancer Research Center. He says that this situation often presents today's brain surgeon with an unenviable decision: choose either to cut aggressively, potentially damaging healthy brain tissue, or cut conservatively and run the risk of leaving tumor cells behind.

Enter T-601, the synthetic version of a chemical first found in the scorpion's sting. Neurobiologist Harold Sontheimer of the University of Alabama at Birmingham, who was the first to explore the medical potential of this chemical, found that it was able to pass into the brain unobstructed. That's a feat for most chemicals, as the membrane that separates the brain from the bloodstream (known as the blood-brain barrier) is notoriously impermeable.

For the scorpion, this property if its venom ensures a quick kill of its unfortunate prey. But subtract the poisonous components from the venom, and you have a perfect vehicle for penetrating the brain.

What's more, researchers have found that this chemical seeks out and binds to brain tumor cells.

Olson says these properties make T-601 a perfect candidate for helping doctors distinguish the borders of brain tumors.

"The scorpion has had millions of years to optimize this chemical that crosses into the brain to damage its prey," he says. "It would have cost drug companies hundreds of millions of dollars to develop something like this."

It's not the first time researchers have eyed this compound as a potential cancer fighter. In 2006, Dr. Adam Mamelak, a neurosurgeon at Cedars-Sinai Medical Center in Los Angeles, sought to exploit these properties by using the chemical to carry tiny bits of radioactive material into the brains of patients who had gone through surgery to have brain tumors called gliomas removed.

The idea was that the chemical would seek out the remaining bits of brain cancer, latch onto them, and destroy them. Preliminary trials in humans showed some success.

And Mamelak says Olson's approach may hold promise where other tagging techniques have failed. "This method has been tried with antibodies for man years with less success due to the large size of antibodies," he notes.

But he adds that there could still be a long way to go before such approaches become a fixture in the clinical setting.

"Unfortunately, while this technology is 'sexy' and visually appealing, it is unlikely to have much impact on cancer treatment in the near future," Mamelak says.

Still, other experts in the area of brain research say Olsen's technique represents an exciting step toward better brain tumor removal.

"This is a very exciting development in the field of tumor cell markers, which can be used to improve a surgeon's ability to identify and remove tumors with surgery," says Dr. Allen Sills, executive director of the Memphis Regional Brain Tumor Center and associate professor of neurosurgery at the University of Tennessee College of Medicine. "A more complete removal of the tumor has been shown to clearly result in longer survival for patients with all forms of brain tumors and may offer hope for curing some types of tumors."

Considering the grim prognosis that often accompanies such tumors, the prospect of longer survival is a welcome one. For the roughly 17,000 Americans who face a glioma diagnosis each year, life expectancy is generally measured in months. On average, fewer than one in 10 is alive after two years. After five years, the figure is more like one in 30.

The dire situation of these patients has led to other novel approaches to differentiate cancerous cells in the brain from healthy ones.

"Several agents are in, or have been in, clinical trials in Europe," says Dr. Gene Barnett, professor and director, of the Brain Tumor and Neuro-Oncology Center at the Cleveland Clinic Neurological Institute. "What all of these techniques have in common is that they should -- and do, for those that have been scientifically tested -- help the surgeon do more complete surgery. More complete surgery may translate to better, longer survival for patients with malignant brain tumor, as long as the surgery can be done safely."

Despite hope and continued development of T-601, however, clinical applications are likely years away.

"A big problem is that the fluorescent dyes that Olson used are not FDA-approved and most are very toxic," Mamelak says. "There are basically very few such dyes that are approved, with relatively little incentive due to the costs of toxicity testing to make this approach financially feasible."

But what if the potential of this chemical could be fully harnessed? Olson says that the chemical may be used not only to detect brain cancer cells, but for early detection of other cancers as well.

"We're learning that many kinds of cancer may be able to be detected using tumor paint," Olson says, noting that in the scenario he imagines, a patient could take a tumor paint pill the night before seeing a doctor. Once this patient arrives at the doctor's office, the doctor could perform a simple scan that could detect even small cancer cells early.

For now, such a scenario remains largely theoretical. Still, Olson continues his research. He is currently planning a trip to Australia to work with a toxin and venom group there to see what other venoms may have the same type of therapeutic potential.

"When this idea was proposed to the National Cancer Institute, it was perceived as highly speculative and ambitious," Olson says. "The families of patients have paid for all this research.

"I think it is a beautiful gift, not only to those who have brain cancer, but as a prospective test for all cancer, if this bears fruit."

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