Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions

2011 | journal article. A publication with affiliation to the University of Göttingen.

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​Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions​
Zibert, J. R.; Wallbrecht, K.; Schon, M.; Mir, L. M.; Jacobsen, G. K.; Trochon-Joseph, V. & Bouquet, C. et al.​ (2011) 
Journal of Clinical Investigation121(1) pp. 410​-421​.​ DOI: https://doi.org/10.1172/JCI41295 

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Authors
Zibert, John R.; Wallbrecht, Katrin; Schon, Margarete; Mir, Lluis M.; Jacobsen, Grete K.; Trochon-Joseph, Veronique; Bouquet, Celine; Villadsen, Louise S.; Cadossi, Ruggero; Skov, Lone; Schon, Michael P.
Abstract
Dysregulated angiogenesis is a hallmark of chronic inflammatory diseases, including psoriasis, a common skin disorder that affects approximately 2% of the population Studying both human psoriasis in 2 complementary xenotransplantation models and psoriasis-like skin lesions in transgenic mice with epidermal expression of human TGF-beta 1, we have demonstrated that antiangiogenic non-viral somatic gene therapy reduces the cutaneous microvasculature and alleviates chronic inflammatory skin disorders Transient muscular expression of the recombinant disintegrin domain (RDD) of metargidin (also known as ADAM-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue High-resolution ultrasound revealed reduced cutaneous blood flow in vivo after electroporation with RDD but not with control plasmids In addition, angiogenesis- and inflammation-related molecular markers, keratinocyte proliferation, epidermal thickness, and clinical disease scores were downregulated in all models Thus, non-viral antiangiogenic gene therapy can alleviate psoriasis and may do so in other angiogenesis-related inflammatory skin disorders
Issue Date
2011
Status
published
Publisher
Amer Soc Clinical Investigation Inc
Journal
Journal of Clinical Investigation 
ISSN
0021-9738

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