Repurposing an Antiparasite Drug to Fight Glioblastoma

Title: Phase II Study Mebendazole in Patients with Recurrent Glioblastoma
Investigator: Gregory Riggins
Grantee:  Johns Hopkins University

In the laboratory, scientists have to be ready for anything – and keep an open mind when the unexpected happens.  Dr. Gregory Riggins, a scientist at Johns Hopkins University, did just that when the laboratory mice he was using to study glioblastoma suddenly stopped developing tumors despite his earnest efforts otherwise.

Because mice generally don’t develop glioblastoma on their own, Dr. Riggins had been implanting aggressive human tumors into the mice to give them human-like brain cancer.  The implantation procedure is usually very effective, so it was unexpected that the mice would suddenly stop developing tumors.  Rather than chalking the problem up to a glitch with the mice or his methods, however, Dr. Riggins recognized the opportunity presented by his failed experiments.  The mice, he recalled, had recently been treated for a common parasite infection.  Was it possible that this antiparasitic treatment had also protected them from developing brain tumors?

Following this hunch, Dr. Riggins gathered a panel of FDA-approved drugs closely related to the medicine his mice had received.  He tested this panel of drugs on new, tumor-laden mice and found that some of the drugs slowed tumor growth and prolonged survival in the mice.  Mebendazole, an antiparasitic drug with a long track record of safe human use, was particularly effective.  With a bit of digging into past scientific reports, Dr. Riggins further found that close relatives of mebendazole had already been studied in preclinical and clinical trials for other types of cancer, where they delayed tumor growth and killed tumor cells.  This train of evidence raised the tantalizing possibility that mebendazole, a drug already approved by the FDA to fight pinworm infections, might be able to do double duty as a glioblastoma therapy.

To test this idea, ABC2 funded a Phase 1 clinical trial of mebendazole in patients with newly diagnosed, high-grade glioma who were already being treated with the standard of care cell-killing drug temozolomide.  This Phase 1 trial was primarily devoted to determining the safety and preliminary efficacy of mebendazole in treating glioblastoma. It has recently been completed – with encouraging results.  Based on the promise of these early results, ABC2 is now working with Dr. Riggins to move mebendazole into Phase 2 clinical trials designed to more rigorously test its efficacy as a potential new glioblastoma therapy. 

If this project is successful, mebendazole could provide a safe, inexpensive, effective glioblastoma treatment with the potential for rapid translation into the clinic.  Because mebendozole has been used around the world for years to treat pinworm infections in children, it offers a particularly enticing opportunity as a treatment for pediatric brain tumors.