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How does CDK2 inhibition affect hearing?
Researchers have now found that inhibiting a particular enzyme protects against noise- or drug-induced hearing loss. This realization has the potential to save the hearing of millions of people worldwide.
The researchers at St. Jude Children's Research Hospital found that inhibiting an enzyme called cyclin-dependent kinase 2 (CDK2) protects against hearing loss caused by noise or medication. The doctors published the results of their study in the English-language journal "Journal of Experimental Medicine".
About 360 million people suffer from hearing loss
In their experiments on mice and rats, the experts were able to determine that CDK2 inhibitors prevent the death of inner ear cells. This could help people avoid hearing loss in the future. According to the World Health Organization, about 360 million people worldwide, including 32 million children, have hearing loss caused by congenital defects or other factors. These factors include, for example, infectious diseases, taking certain medicines, or exposure to excessive noise. However, there are currently no FDA-approved drugs to prevent or treat hearing loss, the researchers say.
Scientists examined more than 4,000 drugs
Physicians have now tested over 4,000 drugs for their ability to protect cochlear cells from the chemotherapy drug cisplatin. Cisplatin is used to treat cancer, but causes irreversible hearing loss in up to 70 percent of patients, explains study author Dr. Jian Zuo from St. Jude Children's Research Hospital.
Kenpulllon is particularly effective
In their study, the researchers identified several compounds that protect cochlear cells from cisplatin. Some of these compounds have already been approved for the treatment of other diseases. Three of the ten most potent compounds were inhibitors of an enzyme called CDK2. One of these CDK2 inhibitors, Kenpulllon, was more potent than four other compounds currently in clinical trials for the treatment of hearing loss.
Injection protected laboratory animals from hearing loss
Kenpaullon injection into the middle ear protected both mice and rats from cisplatin-induced hearing loss. Kenpaullon also protected the hearing of mice from noise up to 100 dB. Given that 100 dB of noise is in the area of noise pollution that affects many people in today's society, Kenpaullon could have significant clinical application in the future in the treatment of noise-induced hearing loss, explains Dr. Zuo.
Results could improve treatment for hearing loss
The robust protection provided by the single local administration of kenpaullon suggests that CDK2 inhibitors can change the clinical prevention and treatment of cisplatin and noise-induced hearing loss in patients, says Dr. Zuo. Changes in treatment regimens, additional optimization of delivery methods through the use of hydrogels, and structural modifications of the compounds via medicinal chemistry could ensure even better results with CDK2 inhibitors in the treatment of hearing loss in humans, the expert adds. (as)