Evidence of protective effects of recombinant ADAMTS13* in humanized model for sickle cell disease.

Sickle cell disease (SCD) is an inherited red blood cell disorder with a worldwide prevalence. Acute vaso-occlusive crisis (VOC) is the main cause of hospitalization in patients with SCD. Growing evidence highlights the key role of inflammatory vasculopathy in both acute and chronic SCD related clinical manifestations. In a humanized mouse model for SCD, we found an increase of vWF activity and a reduction in ADAMTS13/vWF activity ratio similar to that observed in the human counterpart. rADAMTS13 was administered to humanized SCD mice before exposure to hypoxia/reoxygenation (H/R) stress as model of VOC. In SCD mice, rADAMTS13 reduced H/R induced hemolysis and systemic and local inflammation in lungs and kidneys. rADAMTS13 also diminished H/R induced worsening of inflammatory vasculopathy, reducing local nitric oxidase synthase expression. Collectively, our data provide for the first-time evidence that pharmacologic treatment with rADAMTS13 (TAK-755) diminished H/R induced sickle cell related organ damage. Thus, rADAMTS13 might be considered as a potential effective disease-modifying treatment option for sickle cell related acute events.