Intratympanic Treatment of Acute Inner Ear Disorders with AM-111: A New Cell-Permeable JNK Ligand

Abstract

Background and Aim: Acute inner ear disorders like sudden deafness, acoustic trauma, tinnitus, and others are thought to initiate complex biochemical processes in the sensory hair cells that can lead to apoptosis. Apoptosis is an active process that is characterized by chromatin condensations, intracellular fragmentation, and intranucleosomal DNA fragmentation. The molecular mechanism behind it is the JNK (c-Jun N-terminal kinase) group of mitogen-activated protein kinases (MAPK), also known as stress-activated protein kinases. In different animal models, the intratympanic administration of AM-111, a cell-permeable JNK ligand also known as D-JNKI, has been shown to prevent hearing loss after acute acoustic trauma. Functional and morphological analysis of the treated ears revealed excellent otoprotective properties that could be obtained even when AM-111 was administered hours after the noise exposure. Blocking the signal pathway with D-JNKI-1 is therefore a promising way to protect the morphological integrity and physiological function of the inner ear.