WEINHEIM, Germany & RALEIGH-DURHAM, NC, USA I March 11, 2014 I Interim data on the use of liver cell therapy (LCT) for the treatment of pediatric patients with Urea Cycle Disorders (UCD) were presented today at the Annual Meeting of the Society for Inherited Metabolic Disorders (SIMD) in Pacific Grove, California.

UCD is a rare, potentially life-threatening liver metabolism disorder that in its severe form can affect newborns and infants, causing toxic levels of ammonia to accumulate in the body, which can lead to massive and irreversible damage of the nervous system including the brain. For patients suffering from severe neonatal UCD, liver transplantation remains the only option for long term stabilization. However, liver transplantation is still very difficult in small infants and success rates clearly increase in older infants. Therefore, the current goal for Cytonet’s liver cell therapy is to treat severe UCD patients in order to stabilize them until they have reached an age and size that allows liver transplantation to be performed with a high probability of success and/or until a suitable donor organ becomes available.

Thomas Opladen, MD, from the University of Heidelberg presented data from a combined interim analysis of two studies performed in Germany, the U.S. and Canada. Patients less than six months of age with a confirmed diagnosis of UCD (OTCD, CPS1D or ASSD (citrullinemia) were treated with liver cell therapy and were compared to a historical control group treated with the current standard of care. Advantages for the treated group were seen for parameters such as event free survival time or incidence of moderate or severe hyperammonemic events. Reduction of such events is the objective of the liver cell therapy in order to avoid irreversible brain damage. The liver cell therapy was well tolerated.

“The markedly prolonged event free time and the less severe hyperammonemic events after treatment with liver cell therapy are promising and suggest that liver cell therapy may play an important role in managing patient’s ammonia levels,” said Dr. Opladen.

Cytonet’s liver cell therapy involves collecting healthy cells from donated livers not suitable for organ transplantation. These cells are infused into the portal vein in six sessions on six consecutive days. The Company is currently conducting two on-going multicenter clinical trials in U.S. and Canada (SELICA III), and in Germany (SELICA V).

In December 2013, Cytonet submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) seeking approval for its liver cell therapy for the treatment of Urea Cycle Disorders in children.


According to the National Urea Cycle Disorders Foundation (NUCDF), a urea cycle disorder is a genetic disorder caused by a deficiency of one of the six enzymes in the urea cycle which is responsible for removing ammonia from the blood stream. These include carbamoyl phosphate synthetase I (CPS I) deficiency, N-acetylglutamate synthetase (NAGS) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthetase (ASS) deficiency (which is also known as citrullinemia), argininosuccinate lyase (ASL) deficiency and arginase 1 deficiency (hyperargininemia). The urea cycle involves a series of biochemical steps in which nitrogen, a waste product of protein metabolism, is removed from the blood and converted to urea. Normally, the urea is transferred into the urine and removed from the body. In urea cycle disorders, the nitrogen accumulates in the form of ammonia, a highly toxic substance, and is not removed from the body resulting in hyperammonemia (elevated blood ammonia). Ammonia then reaches the brain through the blood, where it causes irreversible brain damage, coma and/or death.

Urea cycle disorders are included in the category of inborn errors of metabolism. Inborn errors of metabolism represent a substantial cause of brain damage and death among newborns and infants. Because many cases of urea cycle disorders remain undiagnosed and/or infants born with the disorders die without a definitive diagnosis, the exact incidence of these cases is unknown and underestimated. It is believed that up to 20 percent of Sudden Infant Death Syndrome cases may be attributed to an undiagnosed inborn error of metabolism such a urea cycle disorder. For more information, please visit NUCDF at www.nucdf.org.


Cytonet is an international biotechnology company which is located in Weinheim and Heidelberg in Germany and in Durham, NC in the U.S. The Company develops and produces cellular products for therapeutic purposes. Cytonet’s goal is to provide alternatives to existing therapies for many diseases with a particular emphasis on liver diseases. Cytonet is a pioneer and leader in the field of regenerative medicine. For the past several years, Cytonet has worked with internationally-leading metabolism and neonatal centers to study its liver cell therapy which uses healthy and metabolically functional human liver cells collected from donated livers not suitable for transplant for infusion to treat urea cycle disorders in children. For more information, please visit Cytonet’s website at http://www.cytonetllc.com/.

SOURCE: Cytonet