Deafness Research Foundation Sponsors Seminal Conference on Cell Replacement in the Inner Ear
A three-day international conference on fundamental research in the emerging fi eld of cell replacement in the inner ear was held in Bethesda, Md., June 13-16, 2008. The first of its kind in more than a decade, the conference was supported by the National Institute on Deafness and Other Communication Disorders, the University of Washington, the Deafness Research Foundation and a grant from the Susan and Sanford Greenberg Foundation.
The meeting was well attended and presented substantial advances in all areas of regeneration biology. Three broad topics were discussed: regenerative biology, cell transplants and genetic manipulation. A fourth area, translational issues, reviewed advances in research methods to support this field, including methods for labyrinthine access and therapeutic delivery. Although it was apparent that much progress has been made, an actual treatment involving cell replacement in humans is a decade or more away.
Sensory disorders of the inner ear occur frequently, affecting people of all walks of life. Inner ear hearing loss results from diverse causes, including genetic disorders, aging, drug and environmental toxicity, trauma, viral infection and idiopathic conditions. Because of the frequency – 36 million Americans have hearing loss and 95 million Americans will complain to their doctors of dizziness at least once in their lifetime – as well as the cost of treatment, habilitation and rehabilitation, these disorders have become a substantial societal burden. The cost of medical care for people with balance disorders alone has been estimated to exceed $1 billion annually in the United States. Hearing and balance disorders increase in prevalence in the older age groups and by age 75 these are among the most common chronic conditions of aging and major reasons the elderly seek healthcare. Sixty-eight percent of military personnel returning from the Middle East have increased hearing loss and 100 percent of those with major body injury have severe hearing loss, tinnitus and imbalance. Clearly these considerations justify renewed and accelerated efforts to restore hearing through biologic means.
Researchers have known for 20 years that birds, fish and amphibians regrow inner ear structures spontaneously after noise or drug damage. The factors that make this possible were discussed at the Cell Replacement Conference. Of the two major cell types in the ear, sensory (hair cells) and supporting cells, it is the loss of hair cells that results from noise and ototoxic antibiotics. After inner ear injury in one of these animals, the supporting cells begin to proliferate and divide, forming new hair cells. In some instances, the support cell becomes a new hair cell through direct transformation but the majority of cells fi rst divide before changing their shape and function. The factors that control these changes were discussed in detail. The helix-loop transcription factor– Atoh1 (also known as Math1 or atonal) – appears to be a key element in these processes.
The mammalian inner ear does not spontaneously recover after injury. To explore why we lack this ability, several mutant mouse models have been developed to permit an analysis of the same factors that work in the bird ear to see if they also play a role in the mouse. Certain types of mutant mice grow a few apparent hair cells but the number is small and the process is not self-sustaining. Many presentations focused on possible methods to overcome the regulatory blockage. Technologies for accessing the human cochlea for possible insertion of genes, transcription factors and stem cells were discussed. While an application for human hearing is years away, restoration of balance function appears to be a surmountable challenge in the next few years.
For more information about the Cell Replacement conference, visit www.drf.org.
