Highly Effective, Innovative Treatment of Acute Liver Failure

Reference Number TO 03-00295

The Challenge

Acute liver failure (ALF) is determined by a fulminant loss of functional cells in a previously healthy and normal functioning liver. It is mainly caused by medicamentous overdosage or viral hepatitis. ALF is a rare disease but for up to 70% of the patients with fatal outcome. At present, no healing therapies exist, only supportive treatment can be offered to the patient when ALF happens, e.g. detoxication via medication or via liver dialysis. For the patients without spontaneous healing of the liver a cost intensive transplantation is necessary. Until now, no therapeutical scheme exists to inhibit the loss of functional liver cells, only the symptoms of ALF can be combated.  

The Technology

Cell death in ALF is caused by the initiation of two signal transduction pathways which lead to apoptosis and necrosis. To inhibit these two signaling pathways an efficient approach has been identified to prevent fulminant loss of liver cells. A chimeric fusion protein has been engineered consisting of two parts, i) a biological active which blocks the pathways, ii) a transport protein part which channels the fusion protein into the liver cells.
Excellent results for the feasibility of this therapeutic approach could be shown in a study with 3 different mouse models for ALF (Jo2, ConA ,GaIN/LPS). Hereby one group of mice got peritoneal application of the chimeric fusion protein before being treated with ALF-inducing stimulants (n=17). The other group got the fusion protein administered after infection with the stimulants (n=17). In both groups all treated mice survived, while the mice of the control groups died. Furthermore the liver of pre-treated mice showed no apparent injury compared to a healthy liver. The data demonstrate the approach of using the chimeric fusion protein has a remarkable therapeutic potential in ALF, mainly because of its cytoprotective effects. Because of the anticipated short duration of treatment with the protein the cancerogenous risk and the risk for developing immunogenecity is supposed to be negligible in this therapeutic approach
 

Commercial Opportunity

The invention can be used to develop a biological drug as curative treatment of ALF 

Patent situation
A priority claiming patent application has been filed in EP in 2009.

Further Reading
A manuscript is under review and can be received under a CDA.

Contact:

Karen Uhlmann, Ph.D.
Technology Manager
Ascenion GmbH

T: +49 (0)30 9406 2301
F: +49 (0)30 9406 2302
uhlmann(at)ascenion.de