Scientists find p27Kip1 protein expression in adult and aged human inner ear

Feb 25 2011

In collaboration with scientists and clinicians from the University of California Los Angeles, scientists from Sound Pharmaceuticals have found p27Kip1 to be expressed in the adult and aged human inner ear including the auditory and vestibular sensory organs. In the adult human inner ear, the pattern of p27Kip1 expression was restricted to the nuclei of supporting cells in the organ of Corti, the sensory organ that controls hearing, and the utricle and cristae, two sensory organs that control balance. These findings are identical to what has been observed and reported in neonatal and adult rodents, further validating p27Kip1 as a key regeneration target in the deafened mammalian inner ear. The fact that p27Kip1 was expressed in the supporting cells of the aged human cochlea from patients over 80 years old suggests that p27Kip1 is still working to suppress proliferative regeneration throughout life and is an appropriate drug target to stimulate supporting cell and hair cell regeneration. These findings were presented at the 34th Annual Midwinter Meeting of the Association for Research in Otolaryngology held this week. This work was supported by the National Institute on Deafness and Other Communication Disorders and the Office of Naval Research.

SPI is developing a proprietary technology for regenerating cells within the inner ear of mammals as a means to restore auditory function to the hearing impaired or deaf. By inhibiting p27Kip1, a cyclin dependent kinase inhibitor or CKI, supporting cell and auditory hair cell regeneration is stimulated in adult mice and Guinea pigs that were previously exposed to intense noise or ototoxic drugs. This novel proliferative and regenerative ability is absent in adult mammals, resulting in permanent and often progressive sensorineural hearing loss, the most common communication disorder and neurologic disease. Current development is focused on the local injection of an inhibitor of p27Kip1 (a p27 siRNA) into the cochlea of deafened adult mammals five weeks after the establishment of permanent hearing loss. The ultimate goal of this novel CKI inhibition technology is to restore hearing to the severe or profoundly impaired.