March 2018 Medical News Today
It is thought that, worldwide, around 466 million people have "disabling hearing loss," which can be caused by a variety of factors — including infection, birth defects, exposure to noise, and the use of some medicines. The researchers behind a new study published in the Journal of Experimental Medicine note that inhibiting an enzyme known as cyclin-dependent kinase 2 could potentially save the hearing of millions of people. Such an inhibitor, kenpaullone, was found to protect rodents from noise- and drug-related hearing loss by preventing the death of inner ear cells. If such CDK2 inhibitors are proven to be an effective treatment for this purpose in humans, it would be very significant, as there are no medicines currently approved by the Food and Drug Administration (FDA) to treat hearing loss.
The researchers examined the individual potential of more than 4,000 drugs to protect inner ear cells from the adverse effects of a chemotherapy drug called cisplatin, which is known to induce hearing loss in up to 70 percent of patients. Although cisplatin is effective against cancer, its associated side effect of hearing loss can be irreversible. Narrowing the list of 4,000 potential treatments down to 10, the scientists found that three of the most effective drugs were CDK2 inhibitors. The most effective of these was a compound called “kenpaullone." The scientists found that injecting kenpaullone into the middle ear of mice and rats protected the animals from the hearing loss associated with cisplatin. In the study, kenpaullone seemed to stop CDK2 from initiating the production of "toxic reactive oxygen species" in the cells of the ear. Toxic reactive oxygen species are molecules and free radicals derived from molecular oxygen that are believed to cause a number of adverse effects to cells. The researchers believe that this is the mechanism by which kenpaullone protected the animals from cisplatin-related hearing loss.
Another interesting finding reported in the study was that kenpaullone also protected mice from hearing loss caused by noise up to 100 decibels. “Given that 100-[decibel] noise is in the range of noise insults commonly experienced by people in our society, kenpaullone could have significant clinical application in treating noise-induced hearing loss."
Lead researcher Dr. Jian Zuo and team believe that the protection conferred to the animals in the study by just one injection of kenpaullone was so powerful that CDK2 inhibitors might "transform the clinical prevention and treatment of cisplatin- and noise-induced hearing loss in patients" — especially if these existing drugs are further optimised specifically for this purpose.