Synthetic version of chlorotoxin shows promise in treatment of brain tumors

A drug developed and tested at University of Alabama at Birmingham targeted at malignant brain tumors known as glioma has shown promising results in a Phase 1 trial, according to results presented at the American Society for Therapeutic Radiology and Oncology annual meeting.

The findings indicate that an intravenous formulation of TM-601 can cross the blood brain-barrier and bind to tumor tissue in the brain.

TM-601 is a synthetic version of chlorotoxin, a naturally occurring peptide derived from scorpion venom. It was developed by scientists at UAB and TransMolecular, Inc., a biotechnology company which funded the current study.

“This Phase 1 study provides important data demonstrating that TM-601 can cross the blood-brain barrier, which is an obstacle in the development of drugs for brain cancer,” said John Fiveash, M.D., associate professor of radiation oncology at UAB and primary investigator of the trial. “TM-601 may emerge as a promising new therapeutic drug for glioma patients, a community with significant unmet needs due to the current lack of drug treatments.”

TM-601 binds with certain receptors on malignant tumor cells in the brain, without affecting nearby healthy cells. As it binds with tumor cells, it can deliver a targeted dose of radiation that kills the tumor cell. Previous studies have involved introducing the drug directly to tumor cells through the skull. Fiveash says the current study was intended to determine if the drug could be delivered intravenously.

“We intravenously administered TM-601 to five patients with recurrent gliomas,” Fiveash said. “All five demonstrated specific uptake of the drug, indicating that it had successfully crossed the blood-brain barrier.”

“Additionally, one patient showed a reduction in the volume of enhancement of the tumor on a MRI scan, suggesting possible tumor response to treatment,” he said. “Since the drug was safe at the tested dose, we anticipate a larger dose may be able to be given without a high risk of toxicity.”

Glioma is a particularly invasive form of brain cancer that does not respond well to current surgical or medical treatment options. There are 36,000 primary brain tumors reported each year, and nearly half are high-grade gliomas. Half of those with high-grade glioma die within the first year.

The discovery that scorpion-based chlorotoxin bound with certain malignant cells in brain tumors was first reported in 1996 by a UAB team led by Harald Sontheimer, Ph.D., professor of neurobiology and director of the UAB Civitan Research Center.

TransMolecular, Inc. is a privately held, venture capital backed biotechnology company committed to discovering, developing and commercializing novel and proprietary products to diagnose and treat cancers that have inadequate treatment alternatives.

NOTE: The University of Alabama at Birmingham is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on second reference.