Efficacy of N-carbamoyl-L-glutamic acid for the treatment of inherited metabolic disorders

ABSTRACT

Introduction: N-carbamoyl-L-glutamic acid (NCG) is a synthetic analogue of N-acetyl glutamate (NAG) that works effectively as a cofactor for carbamoyl phosphate synthase 1 and enhances ureagenesis by activating the urea cycle. NCG (brand name, Carbaglu) was recently approved by the United States Food and Drug Administration (US FDA) for the management of NAGS deficiency and by the European Medicines Agency (EMA) for the treatment of NAGS deficiency as well as for the treatment of hyperammonenia in propionic, methylmalonic and isovaleric acidemias in Europe.

Areas covered: The history, mechanism of action, and efficacy of this new drug are described. Moreover, clinical utility of NCG in a variety of inborn errors of metabolism with secondary NAGS deficiency is discussed.

Expert commentary: NCG has favorable pharmacological features including better bioavailability compared to NAG. The clinical use of NCG has proven to be so effective as to make dietary protein restriction unnecessary for patients with NAGS deficiency. It has been also demonstrated to be effective for hyperammonemia secondary to other types of inborn errors of metabolism. NCG may have additional therapeutic potential in conditions such as hepatic hyperammonemic encephalopathy secondary to chemotherapies or other liver pathology.

KEYWORDS:

• N-carbamoyl-L-glutamic acid
• Carbaglu
• hyperammonemia
• N-acetyl glutamate deficiency
• NAGS
• inborn errors of metabolism
• urea cycle

Declaration of interest

C. Chapel-Crespo and K. Oishi are employees of the Icahn School of Medicine at Mount Sinai. G. A. Diaz is an employee of the Icahn School of Medicine at Mount Sinai and serves on the medical advisory board of Genepeeks and has consulted for SynLogic Therapeutics, Aeglea Biotherapeutics and the Gerson Lehrman Group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This paper was not funded.