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

Adrien A Eshraghi; Mayank Aranke; Richard Salvi; Dalian Ding; John K M Coleman Jr; Emre Ocak; Rahul Mittal; Thomas Meyer

doi:10.1016/j.heares.2018.03.003

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

Hear Res. 2018 Oct:368:86-91. doi: 10.1016/j.heares.2018.03.003. Epub 2018 Mar 7.

Authors

Adrien A Eshraghi¹, Mayank Aranke², Richard Salvi³, Dalian Ding⁴, John K M Coleman Jr⁵, Emre Ocak², Rahul Mittal², Thomas Meyer⁶

Affiliations

¹ Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: aeshraghi@med.miami.edu.
² Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
³ 137 Cary Hall, Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA; Department of Audiology and Speech-Language Pathology, Asia University, Taichung, Taiwan.
⁴ 137 Cary Hall, Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA.
⁵ JohnCo Research, 3109 Mount Carol Drive, San Diego, CA, USA.
⁶ Auris Medical AG, Basel, Switzerland.

PMID: 29573879
DOI: 10.1016/j.heares.2018.03.003

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.

Keywords: AM-111; Acute sensorineural hearing loss; Brimapitide; D-JNKI-1; JNK pathway; Noise trauma.

Publication types

Review

MeSH terms

Animals
Cell Membrane Permeability
Cell-Penetrating Peptides / administration & dosage*
Cochlea / drug effects*
Cochlea / enzymology
Cochlea / injuries
Cochlea / physiopathology
Cochlear Diseases / complications
Cochlear Diseases / drug therapy*
Cochlear Diseases / enzymology
Cochlear Diseases / physiopathology
Cytoprotection
Enzyme Inhibitors / administration & dosage*
Hearing / drug effects*
Hearing Loss, Sensorineural / enzymology
Hearing Loss, Sensorineural / etiology
Hearing Loss, Sensorineural / physiopathology
Hearing Loss, Sensorineural / prevention & control*
Humans
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
JNK Mitogen-Activated Protein Kinases / metabolism
Peptides / administration & dosage*
Prognosis
Risk Factors
Signal Transduction / drug effects

Substances

Cell-Penetrating Peptides
Enzyme Inhibitors
Peptides
JNK Mitogen-Activated Protein Kinases
D-JNKI-1