The EXTHER project area focuses on the development and testing of innovative therapies, in particular those which aim to support the immune system. Novel treatment strategies are developed on the basis of classic extracorporeal technology platforms, such as dialysis and plasma separation. Special emphasis is placed on the development of extracorporeal blood treatment methods for sepsis therapy. Another approach is the development of extension systems for dialysis.
Development of the extracorporeal immune support system (EISS)
Over 18 million people around the world suffer from severe sepsis every year. In Germany alone, up to 60,000 people die from the disease every year. This is why, together with the company Artcline GmbH, the EXIM group has developed and evaluated a cell bioreactor system which can be used to treat sepsis using immune cells (granulocytes) taken from healthy donors. In doing so, the patient's plasma is circulated extracorporeally in a bioreactor with a granulocyte concentrate taken from a donor of a compatible blood group. During this process, bacterial toxins and other inflammatory substances are removed from the blood plasma by means of phagocytosis, allowing the purified patient plasma to be fed back into the patient's bloodstream. Initial clinical results show a clear improvement in patients' cellular immunocompetence, alongside the decrease in bacterial components. Further clinical trials with adjusted parameters are planned for the near future.
This project looks at optimizing the purification of granulocytes, which are required for the extracorporeal immune support system. A key goal here is to extend storage time under currently applicable transfusion medicine conditions. At present, granulocyte concentrates can only be stored for up to 24 hours at 20–24 °C. An increase in the durability of granulocyte concentrates would significantly increase the flexibility of the therapies to be conducted in an everyday clinical setting and also the logistics associated with donations. Furthermore, pure granulocyte concentrations cannot be manufactured at present as the preparation becomes contaminated by a certain amount of erythrocytes and thrombocytes during apheresis. This project therefore also aims to process human blood preparations in such a way that allows the purest granulocyte fraction possible to be obtained and, in turn, optimally used in a clinical and therapeutic context.
Sepsis, also commonly referred to as blood poisoning, is a complex systemic inflammatory response produced by the body. It is usually triggered by bacteria and their toxins when they manage to enter the bloodstream and results in a powerful immune response which is also directed in part against the patient’s own body. In severe cases, the patient becomes highly susceptible to secondary infections and multiple organ failure. Sepsis and its serious forms of progression is becoming more and more prevalent around the world. This explains why severe cases of sepsis still prove fatal in over 50 per cent of cases today, in spite of the various state-of-the-art intensive care options available. It is essential that the disease is diagnosed and effective antibiotic treatment initiated as quickly as possible: this can mean the difference between life and death. In order to improve a patient’s prognosis, various therapeutic approaches such as renal replacement therapy or adsorptive procedures can be introduced in addition to standard treatment. Hemoperfusion is an important adsorptive procedure, whereby the patient’s blood passes extracorporeally through a cartridge containing an adsorbent. The various commercially available adsorbers target either the removal of toxins (lipopolysaccharides) or of inflammatory mediators (cytokines / chemokines), which are increasingly released during the overreaction of the immune system. This type of cytokine adsorber (CytoSorb) was examined in collaboration with the company CytoSorbents Europe GmbH. CytoSorb adsorption columns are approved in Europe as an auxiliary extracorporeal treatment for sepsis. The columns aim to remove pro- and anti-inflammatory messenger substances from the blood during the immediate defense response where possible. As, however, this adsorption is a non-specific process, investigations were carried out into whether and to what extent different medications used in intensive care such as antibiotics and also other substances such as painkillers, sedatives, cardiovascular drugs and anticoagulants are similarly retained by the adsorber. In in-vitro studies it could be shown that the investigated adsorber removes a significant amount of an anticoagulant-inhibitor (rivaroxaban) from the blood. This finding is of direct clinical relevance: patients who take this anticoagulant-inhibitor and require emergency surgery cannot be subjected to surgery before the active agent has been completely excreted from the body – a process that can take up to eight hours. The adsorber could notably reduce this waiting time, thereby gaining valuable therapy time. Further investigations into the removal of various other interesting substance classes are scheduled for 2018.