Posted December 17, 2013
D. Wade Clapp, M.D., Indiana University, Indianapolis
The primary manifestation of the Neurofibromatosis type 2 (NF2) is the development of vestibular schwannomas - non-malignant tumors that form in the region of the auditory vestibular nerve, which transmits sensory information from the inner ear to the brain. As such, most NF2 patients will eventually experience complete hearing loss due to the growth of these tumors. Existing mouse models of NF2 develop tumors in peripheral nerves and spine providing a valuable resource for understanding disease pathogenesis and developing more effective therapeutic drugs. However, these animal models do not fully mirror the hearing loss and vestibular dysfunction commonly found in patients with NF2. Dr. Clapp, recipient of a Fiscal Year 2011 Exploration - Hypothesis Development Award through the Department of Defense Neurofibromatosis Research Program, has developed an NF2 mouse model that appears to form not only intracranial vestibular schwannomas and meningiomas, the most common brain tumors found in individuals with NF2, but to develop progressive hearing loss as well.
Dr. Clapp and his collaborators performed auditory brainstem response (ABR) testing to determine the timeline of hearing impairment in these mice. They have shown that although these mice have no structural defects in the inner ear (cochlea), they develop hearing loss beginning at 8 months of age and this hearing loss grows more severe by 10 months of age; it is functionally equivalent to being unable to hear a normal conversation. This timeline is in agreement with histological analysis of brains from these mice, showing that by 8 months, 100% of the mice develop vestibular schwannomas associated with the proximal spinal nerve and dorsal root ganglion responsible for transmitting nerve impulses for both balance and hearing. Altogether, Dr. Clapp's data suggest that this NF2 animal model will be a valuable tool with which to study disease pathogenesis and novel drugs targeting molecular pathways thought to be important to tumor development in NF2 and associated hearing loss.