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Development of a complex extracorporeal technology for the treatment of multi-organ-failure

Objective

- Development of microspheres for the removal of endotoxins, cytokines TNFalpha and IL-1beta, exotoxin SEB, bilirubin and toxins of liver failure
- Development of biodegradable endotoxin binding microspheres as a tool of higher safety of MDS.
- Development of MDS-device including the optimization of the plasma filter and the establishment of an intelligent software and hardware to accomplish high safety standards and facilitated handling
- In vivo testing and clinical testing of MDS in specific animal models (endotoxin shock and liver failure) and patients suffering from MOF, respectively

Multi organ failure (MOF), very common in septic shock patients of any age, is a multifactorial disease involving nearly all organs and systems of the human being. Its average mortality is in a range of 40-50%, and prognosis has not significantly improved during the last 10 years. The course of MOF is characterized by complex structure, initiated by endotoxins, followed by a cascade-like activation of different cells and systems. The main objective of this proposal is to establish a therapeutically system which is able to influence the multi-factorial pathophysiology at 3 different levels. The first level concentrates on the removal of free soluble endotoxins and exotoxins from blood. The second level is concerned with the removal of the principal cytokines, TNF-a and IL-1 +, by specific adsorbents. Finally, the third level includes the therapy of acute liver failure, including hepato-renal syndrome. This three step concept is based on a very recently introduced blood purification technology: the WMicrospheres based Detoxification System"(MDS). MDS is a newly developed adsorptive technology, based on a simultaneous adsorption/filtration technique, which employs microspheres in the size of 2-4,um. A suspension containing the microspheres is recirculated very rapidly and is mixed into filtrated plasma from the patient, thereby removing undesirable substances. Due to the very efficient structure of the adsorbent particles, only relatively small amounts are required, which can be applied in combinationor in sequence.

The microspheres developed are selective (use of immobilized functional groups) or specific (use of immobilized antibodies) for the removal of endotoxins, exotoxins, TNF-, IL-1 +, live rrelated substances such asphenols, thiols, aromatic amino acids or other lipophilic substances as well as protein bound substances such as bilirubin. The MDS will be designed for continuous use in intensive care units. A plasmafilter specifically designed to offer optimal conditions for continuous filtration is integrated in the blood circuit. Special sensors, the possibleuse of biodegradable microspheres, the application of magnetic microspheres, which can be replaced without any loss of plasma, and the integration of a centrifugal pump to achieve fast recirculation of the microsphere suspension make MDS a high-tech device in blood purification therapy. The system can be combined with continuous filtration in the secondary circuit, removing uraemic substances including other water-soluble toxins in the middle molecular range. In future, additional possibilities such as the use of hepatocytes or other cells could transform MDS into a bioartificial system. The project is an interdisciplinary one, which includes the development of technically very advanced materials and equipment, which will be tested in vivo and clinically during the duration of the project. It also opens new ways of specific blood purification therapy in other fields of medicine such as metabolic, autoimmune or cancer diseases. These ambitious goals can only be achieved by an international cooperation at European level. The project proposal is designed for a fast transfer of the new technology in industrial production, involving clinical testing but also partners with industrial experience. In conclusion, the project offers European industry new perspectives to compete against industries from the USA and Japan by establishing a complete new technology for blood purification therapy.

Coordinator

Donau-Universität Krems
Address
30,Dr. Karl Dorrek Strasse
3500 Krems
Austria

Participants (7)

Fa. Fresenius AG
Germany
Address
6-8,Frankfurter Strasse
66606 St. Wendel
Fraunhofer-Gesellschaft zur Förderungder Angewandten Forschung e.V.
Germany
Address
Kantstraße
14513 Teltow
Ludwig-Maximilians-Universität München
Germany
Address
15,Marchioninistraße
81312 München
Ruprecht-Karls-Universität Heidelberg
Germany
Address
Theodor-kutzer-ufer
68167 Mannheim
UNIVERSITY OF TWENTE
Netherlands
Address
1,Drienerlolaan 5
7522 NB Enschede
UNIVERSITY OF VIENNA
Austria
Address
18-20,Waehringer Guertel 18-20
1090 Wien
University of Strathclyde
United Kingdom
Address
106,Rottenrow
G4 0NW Glasgow