Gene Therapy in the Ear

Genetic and pharmacologic therapy for inner ear disorders

Primary investigator: Dr. Jian Wang, co-investigators Drs. Bance (Department of Surgery) and Robertson (Department of Pharmacology)

We examine the damage and degeneration in the inner ear related to aging, noise exposure and ototoxic drugs, both individually and in combination. We also explore the potential mechanisms of the pathology and develop therapies that might mitigate or reverse the damage and/or degeneration.

Gene therapies against aging, noise and ototoxic drugs have been investigated by using over-expression of the XIAP and NT3 genes, as well as compounds such as flavenoids. Our research has been funded by CIHR and NSERC grants and other research granting agencies for the past 10 years.

Functions of ribbon synapses in the cochlea and the mechanisms for noise-induced damage and repair

We examine the functional basis for a specific type of synapses:

• ribbon synapses between hair cells (the sensory cells of cochleae: the auditory part of inner ear)
• primary auditory neurons (spiral ganglion neurons-SGNs), especially the function of the presynaptic ribbons for signal processing and underlying molecular mechanisms for this function

We also examine the mechanisms of how this synapse is damaged by noise, a common hazardous factor to hearing, as well as the plastic changes after the damage.

Impact of hearing loss on cognitive function and underlying mechanisms

We focus on noise-induced hearing loss and evaluate how hearing loss impacts the cognitive functions in animal models after the hearing loss is established at different ages. We focus on the hippocampus to see how hearing loss damages the neurogenesis there and how this damage is led by the hearing loss.

Current funded research

"Cochlear gene therapy targeting the protection against aging related hearing loss and neuronal degeneration"
Funding: Canadian Institute of Health Research (CIHR)
PI: Jian Wang, Co-PIs: Manohar Bance, George Robertson

"Mechanisms of ribbon synapse function and plasticity"
Funding: Natural Science-Engineering Research Council
PI: Jian Wang, Co-PI: NA