First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

Abstract

Funding information French Ministry of HealthThe medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries.OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys.In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox

Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation

“…However, in the field of kidney transplantation, a medico-economic study (called OXYOP2) is currently comparing the costs of kidney transplantation depending on whether the graft is HOPE or SCS+M101 preserved. This study is the continuation of the OXYOP trial, 17 which showed that the rate of patients necessitating at least one post-transplant dialysis was significantly lower in SCS+M101preserved kidneys compared with HOPE-preserved kidneys (7% vs. 26%, p = 0.038). As a comparison to this 19% difference in delayed graft function (DGF) rates, an international randomised, controlled trial, comparing HOPE or SCS in deceased-donor kidney transplantation 29 reported DGF rates of 20.8% and 26.5% in SCS and HOPE groups, respectively.…”

“…[13][14][15][16] Recently, in a French clinical trial using kidney transplantation from deceased donors, M101 demonstrated safety and efficacy, drastically decreasing the rate of delayed graft function recovery from 26% to 7%. 17 However, M101 performance in cold-stored liver graft remains to be studied.…”

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

“…Interestingly, first M101 use in human clinical trial demonstrated that kidney preservation with M101 solution (1 g/L) before transplantation, improved graft survival and renal function. No immunological/ allergic reactions or infections were reported confirming its absence of cytotoxicity and immunogenicity 38 . This study establishes the cytocompatibility of M101 (1 g/L) in EC as they represent the first line of defense in the periodontium against any foreign aggression 12 .…”

“…S1-S3). The selected concentration used in this study (1 g/L) has already demonstrated positive outcomes in vivo and in clinical trials 33,38 .…”

Combating hypoxemia in COVID-19 patients with a natural oxygen carrier, HEMO2Life® (M101)

“…This molecule has been administered on human for transplantation as an additive in conservative solution [9] , but never directly intravenously (IV), this study revealed the safety of this product considered as a medical device of class III. However, several published preclinical data showed an effective way to transfer oxygen to hypoxia, in particular to the brain, in a study published in the journal of Neurotrauma by the Naval Medical Research Centers on Trauma brain injury animal model.…”