Paper

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing
Christine T. Dinh, Thomas R. Van De Water

Department of Otolaryngology, Cochlear Implant Research Program, University of Miami Ear Institute, University of Miami, Miller School of Medicine, Miami, Fla., USA

Address of Corresponding Author

Audiol Neurotol 2009;14:383-392 (DOI: 10.1159/000241895)

  Key Words

• Cochlea
• Hearing loss
• Apoptosis
• JNK inhibitors
• Antioxidants
• Corticosteroids

  Abstract

The programmed cell death of stress-damaged auditory hair cells can occur through a variety of signal pathways, and therapeutic modalities that block pro-cell-death pathways are being developed and evaluated for hearing preservation. Because of their ability to have both anti-inflammatory and anti-apoptotic actions, corticosteroids have long been used to protect against several types of acute sensorineural hearing loss. Other anti-apoptotic drugs that target the mitogen-activated protein kinase (MAPK)/c-Jun-N terminal kinase (JNK) signal cascade, such as D-JNKI-1 (AM-111) and SP600125, have produced promising results both in vitro and in laboratory animal studies, with AM-111 showing promise in preliminary clinical trials. Antioxidant drugs, e.g. sodium thiosulfate, N-acetylcysteine, and D-methionine, have been shown in animal studies to attenuate permanent threshold shifts in hearing by reducing oxidative stress. In addition to reviewing selected therapeutic trends for the conservation of hearing, we review our experiences with dexamethasone and D-JNKI-1 and report results from our current research.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Prof. Thomas R. Van De Water
Cochlear Implant Research Program
University of Miami Ear Institute
1600 NW 10th Avenue, RMSB 3160, Miami, FL 33136-1015 (USA)
Tel. +1 305 243 5691, Fax +1 305 243 5552, E-Mail tvandewater@med.miami.edu

  Article Information

Published online: November 16, 2009
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 0, Number of References : 68