Inborn errors of metabolism

The project aims at the investigation of small molecules, orally bioavailable drugs, for the treatment of inborn errors of metabolism. We are evaluating the use of small molecules for the treatment of two diseases, AAT deficiency, one of the most common genetic causes of liver disease in children, and pyruvate dehydrogenase complex (PDHC) deficiency. The most common genetic lesion in AAT deficiency results in a mutant protein, which forms aggregates that accumulate within the endoplasmic reticulum, ultimately causing liver injury. We are investigating drugs to increase the cellular clearance of toxic undegraded proteins. For PDHC deficiency, we are currently testing drugs acting on PDHC regulation to enhance the residual enzymatic activity. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.