Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models.

ABSTRACT: Urea cycle disorders (UCDs) are inherited diseases causing recurrent life-threatening metabolic decompensations due to impaired hepatic ammonia detoxification and decreased ureagenesis. Ornithine transcarbamylase (OTC) deficiency (OTCD) is X-linked and the most common and often fatal UCD. In male hemizygous patients, disease severity primarily depends on the pathogenic sequence variant, while in heterozygous females, disease severity also depends on the X-chromosomal inactivation (XCI) pattern. Females with unfavorable XCI predominantly expressing the mutant OTC protein may be severely affected. Here, we investigated a novel treatment strategy for OTCD since there is an unmet need for better therapies. In the first step, we performed a high throughput screening (HTS) using a diversity libr

SUBMITTER: Ramosaj A 

PROVIDER: S-EPMC12107682 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature