Cytonet GmbH & Co. KG, Weinheim
The Cytonet Group is an international biotech company which currently has 50 employees at the company sites in Weinheim/Germany, Heidelberg/Germany and Durham, North Carolina/USA. The company develops and manufactures liver cell therapy products using specially prepared human cells. In this complex procedure developed by Cytonet, liver cells from donor livers are carefully isolated, prepared and cryopreserved under GMP-conditions. The managing directors of the company are Dr. Dr. Wolfgang Rüdinger, Dipl.-Kfm. Michael J. Deissner and Dr. Torsten Hombeck. Cytonet is a spin-off of Roche’s cell therapy division and was founded in April 2000.
Urea Cycle Disorders and Liver Cell Therapy
Urea cycle disorders are severe and potentially life-threatening disorders in the liver’s ammoniak (NH3) metabolism. Urea cycle disorders are genetic disorders caused by mutations that result in a deficiency of one of the five enzymes in the urea cycle. These enzymes are part of a system detoxifying ammoniak resulting from protein metabolism. In people affected by the disease, neurotoxic ammoniak is not metabolized to urea and subsequently excreted. Instead, it accumulates in the blood and tissue and may – depending on the severity of the disease – lead to severe neural and brain damage or even to death. Normal physical and mental development is almost impossible for children with an untreated urea cycle disorder. Since the only curative measure currently available to newborns – transplanting an entire liver or a liver lobe – is highly problematic, and suitable donor organs are also rare, treatment with liver cells, that have been isolated and prepared from donor livers which are not transplanted, has been investigated during the last years.
Cytonet is cooperating closely with leading international neonatological and pediatric metabolic centers in this venture. The ultimate aim is to effectively compensate the metabolic disorders by infusing healthy and metabolically competent human liver cells into the portal vein of the sick child. The project was funded by the German Federal Ministry of Education and Research (BMBF) within the framework of the cluster of excellence competition.
The advantages of the Cytonet’s liver cell product:
The liver cell suspension is prepared by isolating viable human liver cells from livers that are not transplanted. By utilizing an organ that would otherwise be discarded, this donation for research increases the amount of transplantable tissue made available to the medical community.
Treatment with liver cell therapy is manageable invasive and more tolerable than early OLT
Since liver cell suspension is cryo-preserved, it can be stored long-term and is quickly available for treatment after a rapid thawing process.
Comprehensive assessment of donor eligibility including extensive safety testing narrows the risk of transmitting relevant communicable diseases to recipients.
The treated patient’s liver would still be a candidate for additional treatment options a later time, at which point other therapies, such as gene therapy may become available and could ultimately cure the disease.
The Clinical Development Programme
In 2008 the Cytonet clinical development (CCD) programme commenced with the CCD02 trial in Germany. In 2010, Cytonet clinical development program was amplified by a second clinical trial commencing in the US which was extended to Canada in 2012. Both clinical trials aim to investigate the safety and efficacy of the liver cell therapy in neonates and young children suffering from urea cycle disorder. In December 2013, Cytonet submitted a marketing authorization application to the European Medicines Agency (EMA) seeking approval for its liver cell product. In 2015, the CCD02 trial has been completed.