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.
Nicola Brunetti-Pierri is the Head of the TIGEM Translational Incubator, which aims to develop large-scale in vivo preclinical studies for the treatment of different inherited disorders by using standardized and optimized protocols to facilitate translation from the bench to the bedside.
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As a paediatrician and geneticist, the overall goals of my research are to understand how defects in biochemical pathways result in disease and to develop novel therapeutic approaches for inborn errors of metabolism.
Additional Funding
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Oxalosis & Hyperoxaluria Foundation (OHF) - Clinically relevant animal models of Primary Hyperoxaluria Type 3 (2024-2026)
- AFM - Gene therapy for Wolman disease (2022-2023)