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Although benign, these tumors can cause extreme pain and compromise sensory\/motor functions, including hearing and vision. At present, surgical resection is the main treatment modality, but it can be problematic because of tumor inaccessibility and risk of nerve damage. We have explored gene therapy for schwannomas, using a model in which immortalized human NF2 schwannoma cells expressing a fluorescent protein and luciferase are implanted in the sciatic nerve of nude mice. Direct injection of an adeno-associated virus (AAV) serotype 1 vector encoding caspase-1 (ICE) under the Schwann-cell specific promoter, P0, leads to regression of these tumors with essentially no vector-mediated neuropathology, and no changes in sensory or motor function. In a related NF2 xenograft model designed to cause measurable pain behavior, the same gene therapy leads to tumor regression and concordant resolution of tumor-associated pain. This AAV1-P0-ICE vector holds promise for clinical treatment of schwannomas by direct intratumoral injection to achieve reduction in tumor size and normalization of neuronal function.<\/jats:p>","DOI":"10.1089\/hum.2012.094","type":"journal-article","created":{"date-parts":[[2012,11,9]],"date-time":"2012-11-09T16:08:48Z","timestamp":1352477328000},"page":"152-162","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Regression of Schwannomas Induced by Adeno-Associated Virus-Mediated Delivery of Caspase-1"],"prefix":"10.1177","volume":"24","author":[{"given":"Shilpa","family":"Prabhakar","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Taherian","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gianni","sequence":"additional","affiliation":[{"name":"University of Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Conlon","sequence":"additional","affiliation":[{"name":"University of Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fulci","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Brockmann","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Stemmer-Rachamimov","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Sena-Esteves","sequence":"additional","affiliation":[{"name":"University of Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xandra O.","family":"Breakefield","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,11,9]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1916"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.1.71"},{"key":"e_1_3_3_4_1","first-page":"180","article-title":"Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. 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