Urea cycle disorders (UCD) are a group of rare disorders that are categorized as inborn errors of metabolism. These disorders have serious implications, often resulting in irreversible neurological damage or death. Over the years, there has been a tremendous increase in UCD research.
Several research groups, consortiums and multinational collaborations have come forward and joined hands to enhance understanding of these devastating disorders and to offer key inputs about the need for new studies related to UCD.
There are organizations that work with the UCD patient community and offer valuable insights to UCD researchers regarding issues in the diagnosis, treatment and management of this disorder, so as to shift the focus towards key research priorities. They also work with affected people and their families and help them understand how they can help UCD research by actively participating in the clinical studies.
While UCD research is gaining momentum globally, one challenge still remains. Being a rare disorder, recruiting sufficient number of participants for clinical studies is not easy. Some key UCD research groups and consortiums are briefly discussed below.
SELICA III is a clinical trial sponsored by Cytonet, a biotechnology company. It aims to evaluate the efficacy and safety of liver cell therapy in UCD-affected children in the age range of 0 to 5 years. Eligible subjects are children with the following types of disorders:
- Carbamoylphosphate synthetase I deficiency
- Ornithine transcarbamylase deficiency
- Citrullinemia or argininosuccinate synthetase deficiency.
In liver cell therapy, healthy liver cells are isolated and processed before infusing them into the hepatic portal vein every day for 6 days. The phase II trial aims to gauge the safety of this liver cell infusion. The trial is approved by the US Food and Drug Administration.
The Rare Diseases Clinical Research Center (RDCRC) on UCD has about 15 United States (US) based sites and two international sites. It is funded by the National Institutes of Health and has over 50 investigators and staff. The aim of this center is to investigate morbidity, mortality and biomarkers in more than 500 children and adults having UCD across Canada, Europe and the US. It also aims to conduct phase II trials of new UCD drugs to enhance ureageneis in patients and to assess neural mechanisms of injury with the help of novel neuroimaging and neuropsychological testing methods.
The Urea Cycle Disorders Consortium (UCDC) is an international collaboration made up of a group of neuropsychologists, physician scientists, genetic counselors, nurses, patient advocates and research staff. The diverse team works together to enhance the lives of patients affected by UCD. The UCDC has sites in the US, Canada and Europe with experience in diagnosis, treatment and research of UCD. The consortium enables doctors and researchers to join hands and participate in UCD studies and thus plays a key role in enhancing the understanding of the impact of the disorder in the lives of patients, as well as in finding new and better treatment options for UCD.
Children’s National is a global leader in UCD diagnosis, management and research. Renowned UCD experts such as Mark Batshaw, Mendel Tuchman and Marshall Summar are part of this group and work on clinical and research programs related to UCD. Research programs of the Children’s National pertain to the following areas:
- Impact of genotype on the phenotype of UCD patients
- Carbamylglutamate therapy and gene therapy to combat UCD
- Nitrogen metabolism characterization.
The Center for Translational Science and the Center for Genetic Medicine Research collaborate with the RDCRC funded by NIH for UCD research. This center follows up over 500 UCD patients across 15 sites in Europe, Canada, and the US for a 5 year study about the medical and cognitive consequences of the disorder. It also collaborates with pharmaceutical and biotechnology companies to develop more effective drugs and treatment methods for UCD.
Reviewed by Yolanda Smith, BPharm