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.
animal models: porcine
clinical research/practice
complement biology
ischemia reperfusion injury (IRI)
kidney transplantation/nephrology
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
31
05
2020
revised:
17
07
2020
accepted:
06
08
2020
pubmed:
24
11
2020
medline:
22
6
2021
entrez:
23
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33225626
doi: 10.1111/ajt.16265
pii: S1600-6135(22)08438-6
doi:
Substances chimiques
Complement Inactivating Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012-1026Subventions
Organisme : Medical Research Council
ID : G1001197
Pays : United Kingdom
Organisme : Medical Research Council
ID : G100197/1
Pays : United Kingdom
Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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