New Data Presented at the 2014 Joint Garrod and Canadian Newborn and Child Screening Symposium
June 2, 2014
New data on Cytonet’s investigational liver cell therapy (LCT) found it may help temporarily stabilize pediatric patients with Urea Cycle Disorders (UCD) while they await liver transplantation. The study was presented at the 2014 Joint Garrod and Canadian Newborn and Child Screening Symposium in Ottawa, Ontario on May 31, 2014.
UCD comprise a group of rare, potentially life-threatening disorders of liver metabolism that affect newborns and infants. In its severe form it causes ammonia to accumulate in the body, leading to 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.
Liver cell therapy may help keep the patient stable until a liver transplant is possible. It 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. Cytonet currently has two ongoing multicenter clinical trials in U.S. and Canada (SELICA III), and in Germany (SELICA V) exploring the use of liver cell therapy for patients with UCD.
In his presentation, Aneal Khan, MD, lead author and assistant professor of medical genetics and pediatrics at the University of Calgary and Alberta Children’s Hospital in Calgary, Alberta, Canada, shared case reviews of patients participating in the SELICA III trial. Between October 2012 and December 2013, Dr. Khan treated four patients under the age of 3 with Cytonet’s liver cell therapy. All four achieved a period of sustained normalization of ammonia levels within 30 days, though the duration of control varied from patient to patient.
One patient was successfully bridged to solid organ liver transplantation and two are currently stable, awaiting eligibility clearance. One patient died as a result of complications due to the underlying disease prior to organ transplantation.
“After receiving liver cell therapy, all four of our patients showed normal and stable ammonia levels for a period of time – some patients went up to 10-12 months without a single hyperammonemic episode. In patients where a suitable donor organ was found, liver cell therapy was a successful bridge to liver transplant that also helped the patient recieve adequate nutrition to support growth and development,” said Dr. Khan. “The much longer survival of boys with a deletion in the OTC gene after liver cell therapy shows that this approach shows promise in changing the natural history of a disease that has been universally fatal in our population up until now.”
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.
ABOUT UREA CYCLE DISORDERS
According to the National Urea Cycle Disorders Foundation (NUCDF), urea cycle disorders comprise a group of genetic disorders leading to 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 atwww.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 metabolic 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/.