IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis.

Authors: Butti, E  Bergami, A  Recchia, A  Brambilla, E  Del Carro, U  Amadio, S  Cattalini, A  Esposito, M  Stornaiuolo, A  Comi, G  Pluchino, S  Mavilio, F  Martino, G  Furlan, R 
Citation: Butti E, etal., Gene Ther. 2008 Apr;15(7):504-15. doi: 10.1038/gt.2008.10. Epub 2008 Jan 31.
Pubmed: (View Article at PubMed) PMID:18239607
DOI: Full-text: DOI:10.1038/gt.2008.10

Central nervous system (CNS) delivery of anti-inflammatory cytokines, such as interleukin 4 (IL4), holds promise as treatment for multiple sclerosis (MS). We have previously shown that short-term herpes simplex virus type 1-mediated IL4 gene therapy is able to inhibit experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice and non-human primates. Here, we show that a single administration of an IL4-expressing helper-dependent adenoviral vector (HD-Ad) into the cerebrospinal fluid (CSF) circulation of immunocompetent mice allows persistent transduction of neuroepithelial cells and long-term (up to 5 months) CNS transgene expression without toxicity. Mice affected by chronic and relapsing EAE display clinical and neurophysiological recovery from the disease once injected with the IL4-expressing HD-Ad vector. The therapeutic effect is due to the ability of IL4 to increase, in inflamed CNS areas, chemokines (CCL1, CCL17 and CCL22) capable of recruiting regulatory T cells (CD4+CD69-CD25+Foxp3+) with suppressant functions. CSF delivery of HD-Ad vectors expressing anti-inflammatory molecules might represent a valuable therapeutic option for CNS inflammatory disorders.

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CRRD Object Information
CRRD ID: 7829778
Created: 2014-01-24
Species: All species
Last Modified: 2014-01-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.