Study Identifies Repurposed Drug with Potential to Protect Hearing

Study Identifies Repurposed Drug with Potential to Protect Hearing

FDA-approved dabrafenib could be developed on significantly shorter timeline at lower cost

According to the World Health Organization, some 466 million people have disabling hearing loss, a number projected to double by 2050 to affect 1 in 10 worldwide. However, a groundbreaking School of Medicine study has identified a drug with potential to protect against, or treat, hearing loss.

The findings are significant because no such FDA-approved drug currently exists, and the drug shown effective in protecting hearing in animal models in the study, dabrafenib, is FDA-approved for treating cancers in people. Repurposing FDA-approved drugs can significantly reduce the development timeline (by up to 5 to 8 years) and cost (by up to 40%) compared to new chemical compounds.

Permanent hearing loss is a major side effect cancer patients experience after undergoing cisplatin chemotherapy, affecting 40% to 60% of people who receive the treatment. In a paper published by Science Advances, Creighton scientists and students involved in the research found that dabrafenib can be repurposed to prevent cisplatin- and noise-induced hearing loss in mice.

Since dabrafenib has already gone through cancer clinical trials in humans and its side effects are known and relatively minimal, it is a good candidate to advance through hearing clinical trials, said Tal Teitz, PhD, assistant professor in the Department of Pharmacology and Neuroscience, group leader and corresponding author of the study.

“There are many types of hearing loss that are caused by cisplatin treatment, noise exposure, antibiotics and aging. Our idea was that there could be some common cellular pathways between these different forms of hearing loss,” Teitz said. “It’s very exciting that we were able to identify a drug that was effective in protecting against noise- and cisplatin-induced hearing loss.”

“What makes dabrafenib a particularly promising candidate is that it can be taken orally — the least invasive and most cost-effective mode of treatment,” according to Matthew Ingersoll, PhD, the first author of the paper and a postdoctoral fellow. “Existing surgical treatments for hearing loss like cochlear implants are highly invasive and expensive.”

“More studies need to be done, but we are very excited about continuing to study this drug and understand more about its efficacy and how it works to treat hearing loss,” Ingersoll said. “It is incredibly promising research, and I am hopeful it can be used in the future to improve the quality of life for people affected by hearing loss.”

The study is a continuation of research Teitz conducted at St. Jude Children’s Research Hospital with Jian Zuo, PhD, to develop studies on drug therapy for hearing loss. Zuo is now a professor at Creighton and chair of the Department of Biomedical Sciences. Creighton and St. Jude worked collaboratively on the study.

A Creighton graduate, Emma Malloy, BS’19 (now a Creighton medical student), and two undergraduate Creighton students in Teitz’s lab — Lauryn Caster and Eva Holland — contributed research to the study through the University’s Center for Undergraduate Research and Scholarship (CURAS) program and Summer Research program. Caster and Holland have also since been accepted to the School of Medicine.

The study was funded by research grants from the National Institutes of Health, state of Nebraska, Bellucci Translational Hearing Research Foundation, Office of Naval Research, ALSAC, Dialysis Clinic Inc., Dr. and Mrs. R. Ferlic Research Undergraduate Fellowship and the American Hearing Research Foundation.