SBIR-STTR Award

This proposal aims to develop techniques to restore sensory hair cells and thus hearing loss in humans. Loss of the sensory hair cells in the Organ of Corti is thought to be a major cause of hearing deficits. In non-mammalian vertebrates that are able of regenerating hair cells after death or loss a first key step is the renewed proliferative capacity of the non-sensory supporting cells. Supporting cell proliferation gives rise to new functioning hair cells after acoustic trauma or ototoxic drugs. Supporting cell proliferation has never been observed in the mammalian organ of Corti, even after hair cell death or the application of growth factors. The Principal Investigator has recently determined that p27kip1, a cyclin/cyclin-dependent kinase inhibitor, is expressed in the supporting cells of mice from birth and in adulthood. Experiments are proposed to test whether deletion of p27 is sufficient to induce the regeneration of hair cells following drug-induced hair cell death. In addition, the Principal Investigator proposes to test whether deletion of p27kip1 can alter the progressive outer hair cell loss observed in C57B/6J mice that is similar to the patterns of hair cell loss observed in age- related hearing loss in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

The majority of sensorineuronal hearing loss involves the loss of auditory mechanoreceptors called hair cells. Unfortunately, evidence of hair cell regeneration in the postnatal or adult organ of Corti (auditory sensory organ) has never been observed in mammals. We have identified a rather ubiquitous and potent cell cycle inhibitor that when deleted allows the organ of Corti to regenerate some of its hair cells spontaneously. Once more, the organ of Corti of mice containing one copy of the gene and 50% of normal protein levels are capable of auditory hair cell regeneration. Mechanistically, we have the molecular tools to inhibit this protein in wt animals that possess normal copies of the gene. We must determine whether this strategy of "inhibiting a growth inhibitor" can result in renewed supporting cell proliferation, hair cell regeneration and recovery of function in the wt organ of Corti. This methodology may prove useful in stimulating auditory hair cell regeneration as means of regenerating hearing in the hearing impaired. PROPOSED COMMERCIAL APPLICATION: 1. To further develop a therapeutic product for clinical trials that will induce hair cell regeneration and restore hearing in hearing impaired 2. To ultimately sell, sublicense or partrter to produce revenues based on our p27 technology that was exclusively licensed from the FHCRC and SKI.