Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

Autor: Kassimatis T; Renal Unit, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.; School of Immunology and Microbial Sciences, King's College London, London, UK., Greenlaw R; School of Immunology and Microbial Sciences, King's College London, London, UK., Hunter JP; Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Douiri A; School of Population Health and Environmental Studies, King's College London, London, UK., Flach C; School of Population Health and Environmental Studies, King's College London, London, UK., Rebollo-Mesa I; School of Immunology and Microbial Sciences, King's College London, London, UK.; UCB Biopharma, Brussels, Belgium., Nichols LL; School of Immunology and Microbial Sciences, King's College London, London, UK., Qasem A; Renal Unit, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.; Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt., Danzi G; School of Immunology and Microbial Sciences, King's College London, London, UK.; Department of Nephrology, Clinic Hospital, Federal University of Pernambuco, Recife, Brazil., Olsburgh J; Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK., Drage M; Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK., Friend PJ; Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Neri F; Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Karegli J; School of Immunology and Microbial Sciences, King's College London, London, UK., Horsfield C; Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust, London, UK., Smith RA; School of Immunology and Microbial Sciences, King's College London, London, UK., Sacks SH; School of Immunology and Microbial Sciences, King's College London, London, UK.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Mar; Vol. 21 (3), pp. 1012-1026. Date of Electronic Publication: 2020 Oct 01.
DOI: 10.1111/ajt.16265
Abstrakt: The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25 mg would be tested, starting with 10 mg in cohort 1. No significant difference between Mirococept at 10 mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80 mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3 hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80 mg (equivalent to 120 mg in human kidney) that provides a basis for further clinical development.
(© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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