Blocking pro-cell-death signal pathways to conserve hearing.
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.
Dinh
Christine T
CT
Department of Otolaryngology, Cochlear Implant Research Program, University of Miami Ear Institute, University of Miami, Miller School of Medicine, Miami, FL 33136-1015, USA.
Van De Water
Thomas R
TR
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006309:Hearing / Q000187:drug effects; D034381:Hearing Loss / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009925:Organ of Corti / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D016207:Cytokines; D017382:Reactive Oxygen Species