Zheng-Yi Chen
Dr. Chen's laboratory is dedicated to developing treatments for hearing loss, spanning genetic, noise-induced, and age-related forms across all ages. Genetic hearing loss affects over 26 million people worldwide, while age-related hearing loss impacts more than 50% of individuals aged 75 and older. Despite this widespread prevalence, no FDA-approved drugs or biological therapies currently exist to restore hearing. One major focus of our work is gene and editing therapy for genetic hearing loss. We have demonstrated the effectiveness of gene replacement therapy in mouse models of human genetic hearing loss. We have collaboratively conducted the first successful clinical trial of OTOF gene therapy, which restored hearing and speech abilities in children born with complete hearing loss DFNB9. This groundbreaking study paves the way for future human gene therapy trials. Additionally, we developed the first gene editing treatment in a mouse model of human genetic deafness and are conducting multiple preclinical studies with the goal of initiating clinical trials soon. Our efforts continue to expand toward new treatments for various genetic hearing loss.
Another key area of our research is hair cell regeneration. We have shown that reprogramming adult cochlear cells using a drug-like cocktail can regenerate hair cells in vivo. From this work, we identified an FDA-approved drug that provides potent protection against noise-induced hearing loss in both mice and pigs, and we plan to advance this finding into a clinical trial to evaluate its effectiveness in humans. Furthermore, we have discovered critical molecules that promote spiral ganglion neurofiber outgrowth, offering potential treatments for hidden hearing loss caused by synaptopathy in animal models of noise-induced and age-related hearing loss. The molecules are being evaluated for clinical applications.
To translate our research into clinical applications, we have developed essential technologies such as adult cochlea explant culture and innovative inner ear delivery systems. We are also creating human inner ear organoids to better understand inner ear diseases and to screen new therapeutic options.