Adjunct Associate Investigator
Full Professor of Paediatrics, Department of Translational Medicine, University of Naples "Federico II", Italy
Giancarlo Parenti earned his Medical degree in 1980 and completed his residency in Paediatrics in 1984. He trained as a researcher at the Department of Paediatrics, University of Naples “Federico II”, the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, the Netherlands, (1985-86), and at the Institute of Medical Genetics, Baylor College of Medicine, Houston, Texas (1994). His research activity has mainly been focused on inborn errors of metabolism, particularly on lysosomal storage diseases. His research group is currently working on the development of novel therapeutic approaches and biomarkers for these diseases. Giancarlo Parenti is coordinator of a clinical unit for metabolic diseases at the Department of Paediatrics, University of Naples “Federico II” Hospital, the reference centre for these disorders in Campania, and member of the European Reference Network for Metabolic Diseases. In this network Giancarlo Parenti is coordinator of the lysosomal storage diseases subnetwork. Giancarlo Parenti is member of scientific societies, such as the Society for the Study of Inborn Errors of Metabolism; the European Consortium for Pompe Disease; and the Italian Society for the Study of Inherited Metabolic Diseases.
Novel therapeutic approaches for the Treatment of Lysosomal Storage Disorders
We have explored the feasibility of therapeutic approaches for lysosomal storage disorders using pharmacological chaperones. Pharmacological chaperone therapy is based on the use of ligands to prevent misfolding and degradation of mutated proteins. We have provided data supporting the use of pharmacological chaperone therapy in Pompe disease, a rare metabolic myopathy, due to acid alpha-glucosidase deficiency, and in Fabry disease, an X-linked inherited disease due to alpha-galactosidase A deficiency that is associated with progressive, life-threatening manifestations. We have also provided evidence that chaperones are able to enhance the efficacy of the recombinant alpha-glucosidase used for enzyme replacement therapy in Pompe disease with a synergistic effect. We translated our pre-clinical studies on this synergy into a clinical trial and are developing this research to provide a new therapy for this disorder. We are also working on the identification of novel allosteric pharmacological chaperones. Allosteric chaperones improve the physical stability of target enzymes without disrupting their catalytic activity. We have demonstrated that N-acetylcysteine is a novel allosteric chaperone for alpha-glucosidase and we are currently studying additional molecules with chaperone properties.
Identification of novel biomarkers for Pompe disease
Identifying biomarkers of patient conditions and response to therapies is a major issue in the management of rare, chronic muscular disorders. Clinical measures currently available for Pompe disease are generally specific for subsets of patients, require specific medical skills and patient collaboration, and can be influenced by inter and intra-investigator variance. We have already identified several micro-RNAs as potential biomarkers for Pompe disease which may be helpful in monitoring disease severity and progression and the effects of treatments. We are now extending the search for additional biomarkers using metabolomic and proteomic approaches.
Other innovative approaches for the treatment of LSDs
Multiple and diverse secondary events are important players in the pathogenetic cascade of lysosomal storage diseases. We are currently focusing our studies on the characterization of these secondary events (with a particular focus on autophagy, and oxidative stress), and on the manipulation of these events as an additional therapeutic strategy.