Keynote Lecture

Prof. Dr. Thomas Lenarz
Department of Otolaryngology Hannover Medical School

Biological therapies in the hearing system

Background:
Hearing loss is the most frequent sensory disease in human with a wide variety of etiologies and pathophysiology. Recent advances in research have deepened our understanding of the underlying biological mechanisms and subsequently opened new avenues for diagnostics and treatment. Specific therapies for both acute and chronic hearing loss are developed.

Anatomical and physiological basis for biological therapies of hearing loss:
The middle and inner ear are well defined separate anatomical areas which are accessible for a local treatment also in conjunction with established surgical procedures such as cochlear implantation. This allows for highly specific and spacely restricted specific treatments.

Specific biological therapy:
There are three major treatments: drug delivery, gene therapy and stem cell transplantation.

Middle ear:
Specific therapies focus on the reduction of inflammatory processes using anti-infective, anti-inflammatory and antifibrotic drugs. Recent advances focus on mucosa regeneration using cell culture and tissue engineering techniques. The middle ear is also the passway to the inner ear using different drugs to treat mainly acute inner ear hearing loss such as Meniere’s disease, vertigo or sudden hearing loss.

Inner ear:
Pathophysiological mechanisms in acute inner ear disease can be addressed specifically by local application of drugs such as free radical scavengers, anti-inflammatory proteins and osmotic treatment. Chronic inner ear disease has often a genetic origin, which opens the possibility of a specific treatment through gene therapy in order to stop progression of hearing loss or even improve hearing. A further degeneration of neural elements can be prevented or slow down by local application of neurotrophins. Stem cell transplantation opens the avenues towards hair cell regeneration and protection of hearing loss.

Ways of treatment:
The treatment can be either systemic e.g. osmotic therapy or local. A local therapy is either fluid-based using pumps or reservoirs or can be administered in conjunction with implants e.g. drug coated electrodes. Cell-base therapies use either programmed cells or stem cells for autonomous production of biological substances such as neurotrophins or specific gene products. They can be also cells for hair cell regeneration.

Summary:
Biological therapies have been developed out of the better understanding of pathology of hearing loss and open new specific treatment options for both acute and chronic hearing loss.