A new drug has the potential to revolutionize the prevention and treatment of hearing loss resulting from noise, drug toxicity, and possibly aging, researchers at St. Jude Children's Research Hospital claims. The researchers discovered inhibitors of enzyme Cyclin-dependent kinase 2 (CDK2) that may protect people from developing hearing loss, including hearing impairment in the elderly population.
The study's lead author Jian Zuo, PhD told The Hearing Journal, "We have reported a genomic study that identified a predisposition to cisplatin-induced hearing loss (CIHL) among pediatric brain tumor patients (Xu et al., Nature Genetics 2015). While predicting which patients will develop CIHL is important, it is more imperative to develop drugs to prevent CIHL. There are no FDA-approved drugs for hearing loss. It is these thoughts that inspired us to screen for drugs against CIHL."
The researchers developed an approach to mimic mammalian cochlear cell death caused by antibiotics, noise, aging, and cisplatin to discover otoprotectants. Cisplatin is a chemotherapy agent, a treatment for an array of cancers, reported to cause permanent hearing loss in patients.
Examining a bioactive library of more than 4,000 unique compounds of an immortalized cell from a cochlear cell line of a neonatal mouse, study authors found ten compounds with protective effects against cisplatin ototoxicity. Among the top-hit compounds was kenpaullone, an inhibitor of CDK2 and other kinases, which are found in zebrafish, adult mice, and rats. Kenpaullone was found to deter cisplatin- and noise-induced damage.
"Our compounds are protective [not only] against CIHL but also noise-induced hearing loss (NIHL). It is also likely that it protects against age-related hearing loss (ARHL)," Zuo explained. "Both NIHL and ARHL affect a large fraction of the society. Based on our results in an identical assay, our compound exhibits better protection against cisplatin-induced cell loss than four benchmark compounds currently in clinical trials. Therefore we believe that our compound will eventually fare well in future clinical trials."
When asked if the CDK2 inhibitors can help patients with inborn hearing loss, Zuo explained, "Our compounds will protect HL but have not been shown to restore hearing among patients with congenital deafness."
The researchers have filed a patent on the methods and the compositions of the CDK2 inhibitors that are discovered to prevent cisplatin- and noise-induced hearing loss.