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ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

Siân R Kitcher1, Nerissa K Kirkwood1, Esra D Camci2

  • 1Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom.

JCI Insight
|August 9, 2019
PubMed

Insights

A new drug, ORC-13661, protects inner ear sensory hair cells from damage caused by common antibiotics and chemotherapy drugs. This discovery offers hope for preventing drug-induced hearing loss and ototoxicity.

Area of Science:

  • Ototoxicity research
  • Drug discovery
  • Hair cell biology

Background:

  • Aminoglycoside antibiotics and cisplatin are ototoxic, causing sensory hair cell loss and hearing impairment.
  • Current treatments lack effective methods to prevent drug-induced ototoxicity.

Purpose of the Study:

  • To evaluate ORC-13661 as a protectant against ototoxicity from aminoglycosides and cisplatin.
  • To elucidate the mechanism of action for ORC-13661 in preventing hair cell damage.

Main Methods:

  • Utilized zebrafish larvae and mouse cochlear cultures to test ORC-13661 efficacy.
  • Administered amikacin to rats to assess hearing loss prevention.
  • Performed patch-clamp recordings to analyze ORC-13661 interaction with mechanoelectrical transducer (MET) channels.

Main Results:

  • ORC-13661 demonstrated robust protection of hair cells against both aminoglycosides and cisplatin in vitro and in vivo.
  • ORC-13661 dose-dependently prevented amikacin-induced hearing loss in rats.
  • ORC-13661 acts as a high-affinity blocker of the hair cell MET channel, suggesting a protective mechanism.

Conclusions:

  • ORC-13661 is a versatile and promising compound for preventing ototoxicity.
  • The drug's ability to block the MET channel offers a novel strategy against drug-induced hearing loss.
  • ORC-13661 shows potential for cross-species and broad-spectrum ototoxin protection.
Keywords:
Drug screensDrug therapyIon channelsNeuroscienceTherapeutics

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