Towards gene therapy for deafness

Abstract

Many hearing disorders are associated with the damage or loss of sensory hair cells (HC) which can produce a profound and irreversible deafness. Apoptosis pathway is reported to play an important role leading to rapid expansion of the HC lesion after exposure to intense noise. Furthermore, progress made over the last year in understanding molecular mechanisms involved in the proliferative and regenerative capacity of sensory cells in the mammalian inner ear has raised the possibility that targeted therapies might prevent the loss of these cells and preserve the patient's hearing. A first step towards the successful therapeutic exploitation is a better understanding of the different pathways that control survival and proliferation of sensory cells. In this review, we provide an overview of recent findings concerning the possibility to prevent apoptosis in auditory cells. We also show the current knowledge on the molecular mechanisms involved in the potential regenerative behavior of these cells and the progress of gene therapy to prevent deafness noise-induced.

Sound Strategies for Hearing Restoration

“…With over 300 genetic loci implicated in hearing loss and the causative genes identified for about 70 of them, gene therapy is poised for development as a powerful hearing loss remedy (11–13). Many deafness mutations affect hair cell genes, while some affect neurons or supporting cells.…”

Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy

“…Of these, about half are attributed to a genetic basis (Di Domenico et al, 2010). While our understanding of the causes of genetic hearing loss has advanced tremendously over the past 30 years (Petersen and Willems, 2006), treatments have advanced little over this same time period, and currently consist of hearing amplification for mild to severe losses, and cochlear implantation for severe to profound losses (Kral and O'Donoghue, 2010).…”

Transcriptome characterization by RNA-Seq reveals the involvement of the complement components in noise-traumatized rat cochleae

“…To minimize cochlear damage, numerous pharmacological therapies have been studied (Abi-Hachem et al, 2010, Bielefeld et al, 2011, Clifford et al, 2011, Guthrie et al, 2011, Oishi and Schacht, 2011). Moreover, the development of gene therapies is also underway (Kesser and Lalwani, 2009, Di Domenico et al, 2011, Zhai et al, 2011). Further progress toward these therapies requires a better understanding of the molecular pathways responsible for controlling the cochlear degenerative process.…”