Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111)

Adrien Eshraghi, Mayank Aranke, Richard Salvi, Dalian Ding, John K.M. Coleman, Emre Ocak, Rahul Mittal, Thomas Meyer

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea.

Original languageEnglish (US)
JournalHearing Research
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Acute sensorineural hearing loss
  • AM-111
  • Brimapitide
  • D-JNKI-1
  • JNK pathway
  • Noise trauma

ASJC Scopus subject areas

  • Sensory Systems

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    Eshraghi, A., Aranke, M., Salvi, R., Ding, D., Coleman, J. K. M., Ocak, E., Mittal, R., & Meyer, T. (Accepted/In press). Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111). Hearing Research. https://doi.org/10.1016/j.heares.2018.03.003