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

Publication date: Available online 7 March 2018
Source:Hearing Research
Author(s): Adrien A. Eshraghi, Mayank Aranke, Richard Salvi, Dalian Ding, John K.M. Coleman, Emre Ocak, Rahul Mittal, Thomas Meyer
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.



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