Journal
GENE THERAPY
Volume 16, Issue 11, Pages 1373-1379Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.98
Keywords
thrombotic thrombocytopenic purpura; ADAMTS13; adenovirus
Categories
Funding
- Istituto Superiore di Sanita, Roma, Italy
- Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR), Bergamo, Italy
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ADAMTS13 is a plasma metalloprotease that regulates the size of the von Willebrand factor (VWF) multimers. Genetic or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP) in humans. Plasma infusion is the treatment of choice for patients with congenital ADAMTS13 deficiency. However, this practice exposes patients to the risk of infections, allergies and fluid volume overload. The search for alternative treatments is required. Here, we tested the ability of systemically administered adenovirus encoding human ADAMTS13 to restore the deficient protein in the circulation of Adamts13(-/-) mice. Injection of the adenovirus efficiently transduced the liver, kidney, lung, heart and spleen, resulting in the secretion of ADAMTS13 into plasma. A reduced area of thrombi was observed when blood from Ad-ADAMTS13-treated mice was perfused over a collagen-coated surface in a parallel plate flow chamber compared with blood of Ad-beta Gal-treated controls. The secreted ADAMTS13 protein was functionally active even after 2 months from injection. The data provide the proof of principle for developing a novel therapy for the correction of ADAMTS13 deficiency in patients with hereditary TTP. Gene Therapy (2009) 16, 1373-1379; doi:10.1038/gt.2009.98; published online 13 August 2009
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