Dataset Information

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

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-?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.

SUBMITTER: Zibert JR

PROVIDER: S-EPMC3007133 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zibert John R JR Wallbrecht Katrin K Schön Margarete M Mir Lluis M LM Jacobsen Grete K GK Trochon-Joseph Veronique V Bouquet Céline C Villadsen Louise S LS Cadossi Ruggero R Skov Lone L Schön Michael P MP

The Journal of clinical investigation 20101206 1

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-β1, we have demonstrated that antiangiogenic non-viral somatic gene therapy reduces the cutaneous microvasculature and alleviates chronic inflammatory skin disorders. ...[more]

PMID: 21135506

Similar Datasets

Project description:ImportanceUnderstanding the posttreatment prognosis of skin lesions in patients with psoriasis is essential for improving patients' treatment satisfaction.ObjectivesTo model the prognosis of skin lesions for patients with psoriasis after 3 types of therapy.Design, setting, and participantsThis prospective cohort study included patients with psoriasis who visited a dermatologist and were enrolled in the platform of the Psoriasis Standardized Diagnosis and Treatment Center in China from August 2020 to December 2021.InterventionsBiologic, traditional, and systemic therapy for psoriasis.Main outcomes and measuresSkin lesions were measured by the Investigator's Global Assessment (IGA) scale subsumed into 4 stages of severity (IGA 0/1, IGA 2, IGA 3, and IGA 4), with higher scores indicating higher severity. The matching method was used to balance baseline covariates between patients receiving each of the 3 treatments. Transition probabilities from IGA scores at baseline to 0 to 1 month and 1 to 12 months were estimated.ResultsA total of 8767 patients were included in the final analysis (median age, 38.6 years [IQR, 28.7-52.8 years]; 5809 [66.3%] male). Across the 3 therapies, as the follow-up duration increased, the probability of improvement transition into a less severe IGA stage (from IGA 4 to IGA 0/1) increased from 0.19 (95% CI, 0.18-0.21) in 0 to 1 month to 0.36 (95% CI, 0.34-0.37) in 1 to 12 months. Biologic therapy was associated with greater improvement transitions for severe conditions, with transition probabilities from IGA 4 to IGA 0/1 increasing by 0.06 (95% CI, 0.02-0.09) vs traditional therapy and by 0.06 (95% CI, 0.03-0.09) vs systemic therapy in 0 to 1 month and by 0.08 (95% CI, 0.04-0.12) vs traditional therapy and 0.11 (95% CI, 0.07-0.14) vs systemic therapy in 1 to 12 months.Conclusions and relevanceThis cohort study modeling psoriasis prognosis provided a complete prognosis of skin lesions, and biologic therapy was associated with improved prognosis of moderate to severe psoriasis compared with traditional and systemic therapies. The study provides insight on using transition diagrams to assess psoriasis prognosis and to communicate with patients in clinical practice.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets