New therapies for inborn errors of metabolism and Alpha1 antitrypsin deficiency

New therapies for inborn errors of metabolism We are investigating the regulation of urea cycle enzymes and how this knowledge could impact the development of novel therapies for urea cycle disorders. We also use this knowledge to better understand the pathogenesis and for treatment of complex multifactorial diseases. Among inborn errors of metabolism, we are interested in organic acidemias, primary hyperoxalurias and glycogen storage disease besides the urea cycle disorders. We are investigating both gene transfer and small molecule drugs for these disorders. Alpha1 antitrypsin deficiency We have an active research program on the liver disease caused by mutant alpha1-antitrypsin (AAT), one of the most common genetic diseases. We discovered that livers expressing mutant AAT have defective zonation and global metabolic disturbances due to down-regulation of HNF-4-alpha. We are currently investigating the roles of JNK and CHOP in the disease pathogenesis with the goal to develop strategies that could prevent or treat the disease more effectively. The ultimate goal of this research is to translate mechanistic discoveries into the clinical arena via clinical research performed at the Unit of Innovative Therapies for Genetic Diseases of the Federico II University Hospital of Naples. My clinical research includes an active program on liver-directed gene therapy with ongoing phase 1 clinical trials for a lysosomal storage disorder and for an inherited defect of bilirubin metabolism. 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 January 2022 until last budget year, calculated based on the size of the research group.