Integrating Ataxia Evaluation into Tumor-Induced Hearing Loss Model to Comprehensively Study NF2- Related Schwannomatosis - Abstract
NF2-related Schwannomatosis (NF2-SWN) is a disease that needs new solutions. The hallmark of NF2-SWN, a dominantly inherited neoplasia syndrome,
is bilateral vestibular schwannomas (VS), which progressively enlarge, leading to sensorineural hearing loss, tinnitus, facial weakness, and pain that translates
to social impairment and clinical depression. Standard treatments for growing VS include surgery and radiation therapy (RT); however, both carry the risk of
further nerve damage that can result in deafness, facial palsy, blindness, and hemiparesis. The resultant suffering and debility, in combination with the paucity
of therapeutic options, make the effective treatment of NF2-SWN a major unmet medical need. A better understanding of these mechanisms is essential to
developing novel therapeutic targets to control tumor growth and improve patients’ quality of life. Previously, we developed an orthotopic cerebellopontine
angle (CPA) mouse model of NF2-SWN-related VS, which faithfully mimics tumor-induced hearing loss. In this model, we observed that mice exhibit symptoms
of ataxia and vestibular dysfunction. Here, we described our methodology using a panel of 5 tests to evaluate tumor-induced ataxia and how anti-angiogenic
and anti-fibrotic treatments improve coordination and gait. These methods paired with hearing tests allow us to comprehensively evaluate tumor-induced
neurological deficit and evaluate the efficacy of novel therapeutics to improve neurological function.