Therapeutic Function of Glucagonlike Peptide-1 (GLP-1) for Hearing Restoration After Blast Exposure or Traumatic Brain Injury (TBI)
Abstract
A common injury among Service members is permanent hearing loss. While this hearing loss may stem from a number of encounters on and off duty, a primary cause of hearing damage comes from exposure to high-intensity sound or blast waves. Even relatively mild blast waves can cause traumatic brain injury (TBI), an injury increasingly correlated to hearing loss. While the exact mechanisms of blast-induced hearing loss are not fully understood, evidence indicates damage at the neural level may significantly contribute to auditory degradation. The damage appears to occur not only in the brain, specifically the auditory cortex, but also in the neural networks connected to the inner ear or cochlea. Currently, there is no treatment for military personnel who have experienced blast or high-intensity noise-induced hearing loss. However, the research on Alzheimers and Parkinsons diseases in cellular and animal studies demonstrate that an agonist (e.g., protein) known as glucagon-like peptid-1 (liraglutide), an FDA-approved drug prescribed for the treatment of type 2 diabetes, has been shown to protect against and repair neural damage from trauma such as TBI or stroke. Recent clinical research on military personnel also indicates the strong correlation between TBI and hearing loss, but liraglutides potential as a therapy for blast-induced hearing damage has not been tested. To explore whether liraglutide has the therapeutic function to reduce blast-induced hearing damage, we conducted preliminary studies in animals by injection of liraglutide pre- or post-blast exposure. The results of hearing function tests showed obvious improvements in hearing level after 14 days in drug-treated animals, which were also supported by the histology studies of neural activity changes in the auditory regions of the brain. The outcomes from our preliminary studies provide the rationale for this proposed research. Here we propose to directly test liraglutide in chinchillas for its therapeutic efficacy to restore the hearing after blast exposure. Hearing function tests will be performed throughout the experimental time course, and histology studies will be conducted as well on the collected brain samples. Successful completion of this project will provide a treatment for Service members and others exposed to high-level noise environments. Currently, as a proposed animal study, if significant contribution to hearing recovery due to liraglutide is shown, clinical trials would be necessary to determine its efficacy in the human population. Furthermore, the proposed study will look at the benefits of using the drug immediately after blast exposure rather than after permanent hearing damage has set in, limiting the population of potential patients. The drug is already available as a diabetes mellitus therapy drug, so the reduced amount of tests needed to prove its safety to the public is an added benefit. The contributions of this research to the field of hearing restoration would be both in therapy and in mechanism. If the drug does prove useful, this would clearly be a step in preventing blast-related hearing damage. As well, with the mechanisms of the drug and its interaction with protein receptors known, the functionality of the drug would illuminate pathways activated from hearing damage due to blast pressures, what locations in the central auditory system and peripheral system are most susceptible to hearing loss, and the limitations of correctable or preventable hearing damage. As hearing loss may cause a decrease in the quality of life for Service members and members of the American public, researching methods for preventing blast-related hearing damage would have significant value.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910469
Entities
People
- Rong Gan
Organizations
- United States Army
- University of Oklahoma