Chemotherapy-induced ototoxicity is damage to the inner ear that is caused by the side effects of administered drugs. This can lead to permanent hearing loss and/or tinnitus (continuous ringing in the ear) in the patient. Some of the most common kinds of drugs causing ototoxicity are antibiotics and anti-cancer therapeutics such as cisplatin. Cisplatin is commonly used for the treatment of a variety of cancers, including medulloblastoma, neuroblastoma, osteosarcoma, and testicular, ovarian, cervical, bladder, lung, and head and neck cancers and is considered one of the most ototoxic drugs in use. The development of an otoprotective treatment to combat chemotherapy-induced hearing loss would have a significant impact on patient quality of life. This is particularly important when treating children as they are more susceptible to drug induced permanent hearing loss. This Phase I SBIR proposal involves the fabrication of steroid based therapeutic treatments for protection against chemotherapy induced ototoxicity. The specific aims of this proposal present a roadmap towards the early stage development of steroid formulations for intratympanic implantation. The specific aims of this proposal are threefold: First, the initial composition of the therapeutic formulation will be developed to incorporate the desired therapeutic dose. Second, the developed therapeutic formulation will be characterized utilizing in vitro analyses. These studies will produce a lead formulation with known therapeutic dose and predicted dosing duration in vivo. Third, the therapeutic formulation will be characterized using appropriate animal models in order to determine the drug release and efficacy in vivo. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, drug development and drug delivery for the successful development this product. O-Ray scientists have successfully developed therapeutic formulations that are currently being used in the clinic. This includes an intraocular sustained release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for periods of up to 3 years from a single implantation. Phase II of this project will involve completion of a final formulation for a scale up in manufactue in GMP conditions, the testing of stability and sterility of these formulations, and GLP pharmacokinetic animal studies in two species sufficient to lead to an Investigational New Drug Exemption. The completion of this work will ultimately facilitate a collaboration with a corporate partner for the licensing of our developed product.
Public Health Relevance: Chemotherapy induced ototoxicity is damage to the inner ear which leads to significant debilitating side effects, such as permanent hearing loss and/or tinnitus (continuous ringing in the ear) in the patient. Some of the most common kinds of drugs causing ototoxicity are antibiotics and anti-cancer therapeutics such as cisplatin, and the damage to hearing is most severe in pediatric patients. This Phase I SBIR proposal involves the development of steroid based therapeutic treatments for protection against chemotherapy induced ototoxicity.
