The ultimate goal of the project is to transform the treatment of chronic middle ear inflammations in children, and to reduce the reliance on surgery and typmanostomy tubes. To do so, we are developing a first-line topical non-invasive treatment that can deliver therapy to the middle ear without tympanic membrane puncture, surgery, or general anesthesia. Ear infections are the leading cause of child visits to pediatricians. Approximately 20% of children with acute otitis media (AOM) progress on to chronic otitis media with effusion (COME). Surgery and tympanostomy tube placement under general anesthesia for treatment of recurrent AOM or COME is the most common pediatric surgical procedure requiring anesthesia in the United States. There are no effective non-surgical treatments for COME, nor are there any medical treatments that block the progression of AOM to COME. Our system works by using magnetic forces to selectively deliver medical therapy across the intact tympanic membrane and into the middle ear. Systemic steroids have shown short-term effectiveness for treatment of COME, but long term steroid use has major drawbacks and risks and is not recommended clinically by the American Academies of Pediatrics. Our system enables concentrated topical delivery of steroids (and antibiotics) to the middle ear, and will minimize symptoms associated with systemic steroid administration. In this SBIR Phase I we will demonstrate that magnetic delivery of the steroid prednisolone resolves middle ear effusion and inflammation, as compared to systemic steroids and to no-treatment controls. The first phase I aim will investigate the clearance of middle ear effusion, by visual inspection and by quantitative measures of middle ear inflammation (cytokines, inflammatory cell infiltration, etc).
Aim 2 will assess hearing improvement by auditory brainstem response (ABR) measurements.
Aim 3 will verify that topical magnetic delivery reduces steroid concentration in blood serum as compared to systemic administration. All three aims will be carried out in a recognized small animal model of COME (in C3H/HeJ mice). The number of animals in the study has been chosen to achieve ? 95% confidence hypothesis testing for all three aims. In phase II we will examine a second recognized animal model of COME (e.g. chinchilla), and will initiate safety and pharmacokinetic/dynamic (PK/PD) studies. We agree with reviewers that it important for our system to be able to treat both middle ear infections as well as middle ear inflammation and effusion. We are acutely aware of the clinical need to address both aspects and would like to note that we already have an active and funded grant from the FDA's Pediatric Device Consortium at Children's to show that our method can clear middle ear infections. As part of that grant, we have shown that our method can reliably clear middle ear infections in a recognized rodent model of acute otitis media.
Our overall goal is to improve the treatment of children with recurrent and chronic middle ear infections. We shall do so by using a proprietary non-invasive drug delivery system, which will enable treatment of otitis media without the need for ear drum puncture or general anesthesia and its attendant risks. In this SBIR Phase 1 effort we shall continue to focus on demonstrating our treatment for clearing middle ear inflammation and effusion. We agree with the reviewers that it is also critical to examine the effectiveness of our technology in clearing middle ear infections. However, we note that we already have a funded and ongoing grant from FDA's Pediatric Device Consortium at Children's National, and as part of that grant we have shown that we can reliably clear middle ear infections in a recognized rodent model of acute otitis media.
