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Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
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CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

Tal Teitz1, Jie Fang1, Asli N Goktug2

  • 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.

The Journal of Experimental Medicine
|March 9, 2018
PubMed

Insights

Scientists identified kenpaullone, a drug inhibiting cyclin-dependent kinase 2 (CDK2), as a potential treatment for hearing loss. This compound protected against cisplatin and noise-induced damage in animal models, offering hope for preventing hearing impairment.

Area of Science:

  • Oto-pharmacology
  • Molecular Biology
  • Neuroscience

Background:

  • Hearing loss affects 360 million globally due to aging, noise, and toxins.
  • Current treatments lack FDA-approved drugs for prevention or reversal.

Purpose of the Study:

  • To screen small molecules for protective effects against ototoxicity.
  • To identify novel therapeutic targets for preventing hearing loss.

Main Methods:

  • Screened 4,385 small molecules in cochlear cell lines.
  • Tested protective compounds in mouse cochlear explants and zebrafish.
  • Evaluated kenpaullone in cisplatin- and noise-induced hearing loss models in mice and rats.
  • Investigated the role of cyclin-dependent kinase 2 (CDK2) using knockout mice.

Main Results:

  • Identified 10 compounds protecting against cisplatin toxicity.
  • Kenpaullone demonstrated protection in zebrafish, mice, and rats against cisplatin and noise.
  • CDK2-deficient mice showed increased resistance to ototoxicity.
  • Kenpaullone inhibited CDK2, reduced reactive oxygen species, and enhanced cell survival.

Conclusions:

  • Kenpaullone is a promising therapeutic candidate for preventing hearing loss.
  • CDK2 plays a proapoptotic role in postmitotic cochlear cells.
  • Targeting CDK2 may offer a novel strategy for hearing loss treatment.

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