Small Molecule Therapeutics for Hair Cell Regeneration After Noise Damage
Abstract
Currently, there is no treatment for military personnel who have experienced noise-induced hearing loss. Non-mammalian vertebrates (i.e., chicken, fish, and frog) can spontaneously regenerate hearing sensory cells from their surrounding supporting cells after an injury caused by noise; however, adult mammals cannot. The reason that these hearing sensory cells are not redeveloped in adult mammals is that the mammalian auditory sensory organ, the cochlea, does not have plasticity to regenerate. Our recent genetic studies have changed this long-held paradigm in that we were able to turn non-sensory cells into sensory cells in adult murine models. While a gene therapy clinical trial (phase I) has been approved by the Food and Drug Administration for hearing restoration in deaf patients, our results suggest that other genes perform better, and small molecule drugs targeting these novel genes can be developed for hearing restoration in the adult mammalian cochlea. Excitingly, we discovered a series of proprietary small molecule drugs that specifically target these novel genes and have the potential to promote sensory cell regeneration in the adult cochlea that mimics the gene therapy. Here we propose to directly test these drugs in murine models for their efficacies to restore hearing after noise injury. The drugs will be delivered locally through the ear drum into the middle ear, thus diffusing into the cochlear fluids, a method that is effective and commonly used for treating several middle and inner ear diseases in humans and avoids toxicity commonly associated with many other systematic drug delivery methods. Successful completion of this study will provide proof of concept for further studies to advance these drug candidates into Investigative New Drugs (IND) and eventually clinical trials in patients with noise injury, a process that normally takes 10 to 15 years. These studies will provide the first promising drug candidates to restore hearing among Service men and women who have experienced noise-induced hearing loss. Noise-induced hearing loss is prominent among Service members who will benefit the most from this study. Therapies that regenerate hearing sensory cells to restore hearing may provide Service men and women the opportunity to continue their careers in the military and could be better alternatives to hearing aids and other mechanical devices. These therapies may also reduce the number of Service members receiving disability payments for service-related hearing disabilities and will enhance communication between family members, reduce depression, and decrease anxiety.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810442
Entities
People
- Jian Zuo
Organizations
- Creighton University
- United States Army