Scientists at the Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Institute in Los Angeles say that a key ingredient found in the Giant Yellow Israeli scorpion, TM-601, can transport radioactive iodine to cancerous glioma cells in the brain.   A Phase I study has been concluded using a synthetic version of the peptide which is found in this scorpion’s venom.

Glioma is an extremely aggressive and deadly form of brain cancer. TM-601 binds to glioma cells and has the unusual ability to pass through the blood-brain barrier that blocks most substances from reaching brain tissue from the bloodstream.

Dr. Adam N. Mamelak, M.D., a neurosurgeon at Cedars-Sinai and leader of the Phase I trial, believes TM-601 can be used with other therapies.  The peptide has not affected neighboring tissue or other body organs, and the clinical trial has been shown to be safe on the 18 patients in Phase I.

Mamelak explains “We’re using the TM-601 primarily as a carrier to transport radioactive iodine to glioma cells, although there are data to suggest that it may also slow down the growth of tumor cells. If studies continue to confirm this, we may be able to use it in conjunction with other treatments, such as chemotherapy, because there may be a synergistic effect. In other words, TM-601’s ability to impede cancer growth could allow us to reduce the dose of chemotherapy to achieve a therapeutic effect.”

Doctor Keith L. Black said “Despite advances in surgical technology, radiation therapy and cancer-killing drugs, length of survival has remained virtually unchanged for patients with gliomas. Only in the recent past have we begun to discover some of the molecular, genetic and immunologic mechanisms that enable these deadly cancer cells to evade or defy our treatments, and we are developing innovative approaches, such as this one, that capitalize on these revelations.” Black is director of the Maxine Dunitz Neurosurgical Institute and interim chair of Cedars-Sinai’s Department of Neurosurgery.

Phase II is underway and will assess the effectiveness of multiple doses. The Phase I trail found the median length of survival for all patients was 27 weeks.  Two patients, women in their early 40s, had a “complete radiographic response,” meaning there was no evidence of residual tumor according to magnetic resonance imaging scans. The patients were still alive beyond 33 and 35 months after surgery, despite the low dose of TM-601 and radiation levels that were below expected therapeutic levels.

Analyses also showed that most of the radioactivity delivered by the drug left the region within 24 hours of administration. That which lingered was “tightly localized to the tumor cavity and surrounding regions, suggesting discrete binding to the tumor.” The drug was eliminated primarily through the urine, with radiation doses to the thyroid and other vital organs remaining extremely low and harmless.