Areas of Research: Cochlear Development and Repair, Noise induced Hearing Loss, Neuron Survival and Repair, Mechanisms of Neurite Growth; Drug Discovery
Spiral ganglion neurons carry sound information from the hair cells in the cochlea to the cochlear nucleus in the brain stem. Anything that interferes with the survival or health of these bipolar neurons will interfere with the transmission of sound information and will affect hearing. Damage can be primary or secondary, can be caused by trauma, noise, ototoxic drugs and chemicals and can include loss of synapses, loss of nerve fibers, and cell death. Remarkably, the centrally oriented nerve fibers degenerate more slowly than the peripherally oriented fibers, and can maintain a semblance of their organized arrangement in the cochlear nucleus even when the peripheral fiber has lost its connection to the hair cells. This organization in the brain stem, called “tonotopic” is important for the faithful representation of different frequencies of sound, and its maintenance is important for understanding speech. Not only can spiral ganglion neurons carry information from hair cells to the brain, but in the absence of hair cells, they can also carry information encoded by cochlear implants.
Hearing loss is a much bigger problem than most of us want to believe. According to the National Institute for Deafness and Other Communicative Disorders (NIDCD), approximately 17% of American adults report some degree of hearing loss. And it only gets worse with age. By the time we reach age 75 or older, 47% of us will have a hearing loss.
My laboratory is actively engaged in a research program ultimately aimed at developing drugs to maintain survival of spiral ganglion neurons and to stimulate their nerve fiber regrowth. Survival of spiral ganglion neurons is essential for the functions of both hearing aids and cochlear implants. Regrowth of nerve fibers toward hair cells, either surviving or future regenerated cells, will be essential to reconnect sound information through endogenous neurons. And further, it is thought that regrowth of spiral ganglion peripheral nerve fibers toward a cochlear implant would permit the development of implants with better frequency selectivity and lower power consumption. At this time, as far as we know, there are currently no drugs approved anywhere in the world to maintain neuronal survival and stimulate nerve fiber regrowth in the human cochlea.
We have developed a novel pre-screening procedure that will allow us to evaluate thousands of drugs and compounds for their effects on spiral ganglion neuronal survival and neurite length. The procedure uses cultures of dissociated newborn mouse spiral ganglia, immunolabeling, automated imaging and computer assisted neurite length measurements. The goal is to narrow down the very large field of potential compounds to a few of the most promising that we can then advance to intense examination in an animal model of noise induced hearing loss. In addition, promising compounds can give information on the mechanisms of neurite growth. We recently identified a class of compounds that increases neurite length in vitro, without causing neuronal cell death. We have advanced one compound, fluvastatin to evaluate in a guinea pig model of noise induced hearing loss and found that when delivered at the same time as noise, fluvastatin protects hearing from noise induced hearing loss.