Preclinical assessment of HEMO2life® supplementation for marginal kidney preservation: comparison between static cold storage and machine perfusion – HEMO2Perf

Solid organ transplantation has become an accepted and viable treatment option for end-stage organ failure. Over one million people worldwide have had their lives saved or their quality of life improved by an organ transplant. However, the number of organ donors has been falling for at least a decade, while the number of people awaiting an organ has been rising every year. Several solutions have been proposed to increase the pool of organs amongst which the use of extended criteria donors and better organ preservation protocols to reduce ischemia reperfusion injury (IRI). Indeed, during transplantation, the organ is subjected to a sequence of ischemia (linked to the organ’s removal from the donor circulation and to hypothermic preservation) and reperfusion (linked to the implantation in the recipient) which induces lesions and dysfunctions favoring acute rejection, delayed graft function and the onset of chronic rejections.

Two hypothermic preservation modes of kidney grafts are currently employed: static cold storage (CS) and machine perfusion (MP). MP is more expensive than static CS. In France, health agencies require MP to preserve kidneys obtained from donor deceased after cardiac death The principle of hypothermic preservation is based on metabolism reduction with temperature lowering, however even slow metabolism requires O2; but, none of the existing solutions are capable of providing oxygen to preserved organs, a fundamental element for organ survival involved in IRI.
This research and development project focuses on organ’s oxygenation during preservation by either static CS or MP to prevent IRI and aims at improving the existing preservation solutions in order to improve the quality of kidneys obtained from extended criteria donors. This will be achieved using an extracellular hemoglobin HEMO2life® developed and GMP produced by Hemarina SA. This therapeutic molecule derived from the marine invertebrate Arenicola marina has peculiar properties for organ preservation as it has a high oxygen affinity, an ability to function at low temperatures and an anti-oxidative activity. HEMO2life® is designed as an entrant to all commercial preservation solutions. Preliminary experiments showed that HEMO2life® provided major protective effects against ischemia in a porcine model of standard criteria kidney transplantation using the 2 most common preservation solutions. A manuscript compiling all the data obtained is currently in press. A registration file will be submitted in 2011 to the French regulatory health authorities (AFSSAPS) to commercialize this PTA (“Produit Thérapeutique Annexe”), a status not requiring human trials before market release.

Taking into account the benefits of HEMO2life® supplementation for static CS of standard criteria grafts and the lower costs of HEMO2life® supplementation in CS in comparison to MP alone, we will compare the preservation efficiency of HEMO2life®+CS with the classical protocol of MP preservation in a porcine model of extended criteria donors. This would offer a cheaper and simpler alternative to MP. In addition, we aim at demonstrating that HEMO2life® is also able to improve the function extended criteria kidneys preserved by MP using the same model. In both cases, we will characterize the protective mechanisms involved.
On the short term, this project is designed to bring all the required data to recommend HEMO2life®+CS instead of MP to preserve extended criteria organs or to improve MP preservation, leading to the extension of claims to use this product as a PTA for CS or/and MP for this type of organs. On the long-term, this project aims at substantially improving transplanted organ quality leading to increases in transplantation success rates.
This project fulfills the objectives of the Biomedicine Agency in terms of increasing the donor pool, the key issue of societies such as the Société Francophone de Transplantation or the Société de Néphrologie.