Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

Summary

Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.

Timeline

Start

2010-12

Primary completion

2012-08

Completion

2012-08

Outcome

Outcome not reported

Stopped (Business): “Lack of funding”

Publications

• Results Ah Mew N, McCarter R, Daikhin Y, Nissim I, Yudkoff M, Tuchman M. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Pediatrics. 2010 Jul;126(1):e208-14. doi: 10.1542/peds.2010-0008. Epub 2010 Jun 21.
• Results Yudkoff M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, Payan I, Tuchman M. Measuring in vivo ureagenesis with stable isotopes. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S37-41. doi: 10.1016/j.ymgme.2010.02.017. Epub 2010 Feb 26.
• Results Ah Mew N, Payan I, Daikhin Y, Nissim I, Nissim I, Tuchman M, Yudkoff M. Effects of a single dose of N-carbamylglutamate on the rate of ureagenesis. Mol Genet Metab. 2009 Dec;98(4):325-30. doi: 10.1016/j.ymgme.2009.07.010. Epub 2009 Jul 14.
• Results Tuchman M, Caldovic L, Daikhin Y, Horyn O, Nissim I, Nissim I, Korson M, Burton B, Yudkoff M. N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers. Pediatr Res. 2008 Aug;64(2):213-7. doi: 10.1203/PDR.0b013e318179454b.

Drugs

Indications