Hume Lab

Virginia Merrill Bloedel Hearing Research Center

Department of Otolaryngology-Head and Neck Surgery

Molecular Therapeutics of Hearing Loss

Hearing loss is the most common human disability, affecting over 28 million Americans, about 10% of the population. While hearing aids and cochlear implants keep us connected with the world around us, neither treatment can replace the sensitivity and specificity of the healthy inner ear. The long term goal of our research is to develop biological therapies for hearing loss and dizziness. .

Most hearing loss in children and adults is caused by the loss of inner ear cells or damage to the hearing nerve. In some cases, these cells do not form properly because of genetic abnormalities or they are lost due to aging, noise damage, toxins or disease. Because these cells are not regenerated in mature mammals, this damage results in deafness. Over the past decade, there has been rapid progress in identifying the genes involved in normal hearing and many forms of inherited hearing loss. Some of these genes control the development of the inner ear, while others may block cell growth that might lead to repair of a damaged organ in other tissues. We are optimistic that this knowledge will eventually allow design of new approaches to cell replacement and repair in the inner ear for treatment of hearing loss, tinnitus and dizziness.

Our laboratory is conducting research in three primary areas:

Hair Cell Regeneration

We are interested in developing new therapies that stimulate biological repair or regeneration in the inner ear. Work from a number of laboratories over the past decade has shown that normal patterning of cell types in the inner ear during embryogenesis is controlled by a cascade of genetic "switches" called transcripiton factors. We hypothesize that components of this cascade can be potentially be manipulated in the mature inner ear to regenerate missing or damaged cell types.

Postnatal Auditory Neuron Targeting

The hearing nerve connects the sensory hair cells in the inner ear to the brain in a very precisely ordered map (tonotopicity). This map” is the basis for our ability to discriminate very closely related pitches or frequencies of sound and is established early in the embryologic development of the inner ear. Our laboratory is studying how this map is formed using animal model systems to identify the molecules that control the growth of auditory nerve fibers. Our hope is that we can use these molecules to re-target damaged hearing nerves to cochlear implant electrodes or regenerated hair cells.

Inner ear Viral Gene Delivery

We are establishing surgical techniques to deliver therapeutic molecules, such as viruses for gene therapy, to the adult inner ear. Our initial goal is to optimize safe procedures that target the correct region of the inner ear and do not cause further damage to hearing or balance. We will then be poised to test the beneficial effects of new treatments developed based on studies of hair cell regeneration and hearing nerve fiber targeting.

Acknowlegements

Our research is generously supported by the NIDCD/NIH, Veterans' Hospital Administration and the Hearing Regeneration Initiative. Our work is highly collaborative and involves many colleagues at the Virginia Merrill Bloedel Hearing Research Institute and the University of Washington Medical Center.

A recent UW TV program featured our research on hearing regeneration. "Hearing Loss: Molecular Therapy"