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The hallmark of NF2-SWN, a dominantly inherited neoplasia syndrome, is bilateral vestibular schwannomas (VSs), 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 VSs include surgery and radiation therapy (RT); however, both carry the risk of further nerve damage that can result in deafness and facial palsy. 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\u2019 quality of life. Previously, we developed the first orthotopic cerebellopontine angle mouse model of VSs, which faithfully mimics tumor-induced hearing loss. In this model, we observed that mice exhibit symptoms of ataxia and vestibular dysfunction. Therefore, we further developed a panel of five tests suitable for the mouse VS model and investigated how tumor growth and treatment affect gait, coordination, and motor function. Using this panel of ataxia tests, we demonstrated that both ataxia and motor function deteriorated concomitantly with tumor progression. We further demonstrated that (i) treatment with anti-VEGF resulted in tumor size reduction, mitigated ataxia, and improved rotarod performance; (ii) treatment with crizotinib stabilized tumor growth and led to improvements in both ataxia and rotarod performance; and (iii) treatment with losartan did not impact tumor growth nor ameliorate ataxia or motor function. Our studies demonstrated that these methods, paired with hearing tests, enable a comprehensive evaluation of tumor-induced neurological deficits and facilitate the assessment of the effectiveness of novel therapeutics to improve NF2 treatments.<\/jats:p>","DOI":"10.3390\/cancers16111961","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T06:54:09Z","timestamp":1716360849000},"page":"1961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrating Ataxia Evaluation into Tumor-Induced Hearing Loss Model to Comprehensively Study NF2-Related Schwannomatosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Simeng","family":"Lu","sequence":"first","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Yin","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Sun","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Clinical Research for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Gao","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-6493","authenticated-orcid":false,"given":"Peigen","family":"Huang","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Jordan","sequence":"additional","affiliation":[{"name":"Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-6419","authenticated-orcid":false,"given":"Scott","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-4-16","article-title":"Neurofibromatosis type 2 (NF2): A clinical and molecular review","volume":"4","author":"Evans","year":"2009","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/00129492-200501000-00016","article-title":"Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: Higher incidence than previously thought","volume":"26","author":"Evans","year":"2005","journal-title":"Otol. 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