Document Detail


Regression of schwannomas induced by adeno-associated virus-mediated delivery of caspase-1.
MedLine Citation:
PMID:  23140466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Schwannomas are tumors formed by proliferation of dedifferentiated Schwann cells. Patients with neurofibromatosis 2 (NF2) and schwannomatosis develop multiple schwannomas in peripheral and cranial nerves. 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.
Authors:
Shilpa Prabhakar; Mehran Taherian; Davide Gianni; Thomas J Conlon; Giulia Fulci; Jillian Brockmann; Anat Stemmer-Rachamimov; Miguel Sena-Esteves; Xandra O Breakefield; Gary J Brenner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-30
Journal Detail:
Title:  Human gene therapy     Volume:  24     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-09-10     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  152-62     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspase 1 / administration & dosage*,  genetics,  metabolism
Dependovirus / genetics,  metabolism*
Genetic Therapy / methods*
Genetic Vectors / genetics,  metabolism*
Green Fluorescent Proteins / metabolism
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Neurilemmoma / metabolism,  prevention & control,  therapy*
Neurofibromatosis 2 / pathology,  therapy
Plasmids / genetics,  metabolism
Promoter Regions, Genetic
Psychomotor Performance
Schwann Cells / pathology*
Sciatic Nerve / metabolism,  pathology
Transgenes
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
NS24279/NS/NINDS NIH HHS; R01 NS081146/NS/NINDS NIH HHS; S10 RR025504/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
147336-22-9/Green Fluorescent Proteins; EC 3.4.22.36/Caspase 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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