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

Kassimatis, Theodoros; Greenlaw, Roseanna; Hunter, James; Douiri, Abdel; Flach, Clare; Rebollo‐Mesa, Irene; Nichols, Laura; Qasem, Anass; Danzi, Gian Battista; Olsburgh, Jonathon; Drage, Martin; Friend, Peter J.; Neri, Flavia; Karegli, Julieta; Horsfield, Catherine; Smith, Richard A.; Sacks, Steven

doi:10.1111/ajt.16265

Cited by 23 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further exploration in a porcine study revealed that the failure of the EMPIRIKAL study was due to insufficient Mirococept exposure. The optimal dosage was later determined to be 80 mg for pig kidney experiment, equivalent to 120 mg in a human setting, with efficient therapeutic effects and no obvious side effects (94). Further investigation is needed to explore the efficacy of ex vivo Mirococept delivery in kidney transplant.…”

Section: Ex Vivo Inhibition Of Complement Activation To Prevent Dgfmentioning

confidence: 99%

Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application

Qin

2022

Front. Immunol.

View full text Add to dashboard Cite

Kidney transplantation is a life-saving strategy for patients with end-stage renal diseases. Despite the advances in surgical techniques and immunosuppressive agents, the long-term graft survival remains a challenge. Growing evidence has shown that the complement system, part of the innate immune response, is involved in kidney transplantation. Novel insights highlighted the role of the locally produced and intracellular complement components in the development of inflammation and the alloreactive response in the kidney allograft. In the current review, we provide the updated understanding of the complement system in kidney transplantation. We will discuss the involvement of the different complement components in kidney ischemia–reperfusion injury, delayed graft function, allograft rejection, and chronic allograft injury. We will also introduce the existing and upcoming attempts to improve allograft outcomes in animal models and in the clinical setting by targeting the complement system.

show abstract

Section: Ex Vivo Inhibition Of Complement Activation To Prevent Dgfmentioning

confidence: 99%

Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application

Qin

2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Mirocept, still in a phase 1 trial (ISRCTN49958194)[ 26 ], is a potent membrane-localizing complement inhibitor and may be administered ex vivo to the donor kidney prior to transplantation. However, a recent dose finding study in animals[ 27 ] documented that a high dose of Mirocept might be needed to achieve adequate complement inhibition. More promising results have been obtained with C1 esterase inhibition.…”

Section: Therapy For Dgfmentioning

confidence: 99%

Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Salvadori¹,

Tsalouchos²

2022

WJT

View full text Add to dashboard Cite

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries, new innovative drugs in kidney transplantation are difficult to be encountered. The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market. These unmet needs are the prevention of delayed graft function (DGF), the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection. These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts. The first are particularly exposed to DGF, the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur. Particular caution is needed in treating these drugs. First, they are described in very recent studies and the follow-up of their effect is of course rather short. Second, some of these drugs are still in an early phase of study, even if in well-conducted randomized controlled trials. Particular caution and a careful check need to be used in trials launched 2 or 3 years ago. Indeed, is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.

show abstract

“…The clinical translation of these rodents’ analysis recently led to a multicentre randomized controlled trial, in which Mirococept is administered ex vivo to deceased donor kidneys. The trial, called EMPIRIKAL, aims to evaluate the efficacy of Mirococept in reducing the incidence of DGF in renal transplants from deceased donors ( 74 , 75 ) and provided evidences on safety and feasibility of this new drug.…”

Section: From Brain Death To Renal Ischemia Reperfusion: Molecular Mechanisms Of Graft Damage Brain Death Cold Ischemia Time and Donor Chmentioning

confidence: 99%

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

et al. 2021

View full text Add to dashboard Cite

Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on development of innovative and dynamic preservation techniques, in order to assess graft function and promote regeneration by pharmacological intervention before transplantation. This review provides an overview of the current knowledge of these new preservation strategies by machine perfusions and pharmacological interventions at different timing possibilities: in the organ donor, ex-vivo during perfusion machine reconditioning or after implementation in the recipient. We will report therapies as anti-oxidant and anti-inflammatory agents, senolytics agents, complement inhibitors, HDL, siRNA and H2S supplementation. Renal delivery of pharmacologic agents during preservation state provides a window of opportunity to treat the organ in an isolated manner and a crucial route of administration. Even if few studies have been reported of transplantation after ex-vivo drugs administration, targeting the biological pathway associated to kidney failure (i.e. oxidative stress, complement system, fibrosis) might be a promising therapeutic strategy to improve the quality of various donor organs and expand organ availability.

show abstract

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

Cited by 23 publications

References 25 publications

Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application

Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application

Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

Contact Info

Product

Resources

About