SMALL MOLECULE-BASED THERAPIES WITH FOR LYSOSOMAL STORAGE DISEASES

The aim of the research

Main researcher GIANCARLO PARENTI

The general aim of the project is to identify novel therapies for lysosomal storage diseases (LSDs), a group of genetic disorders due to the deficiency of enzymes involved in the degradation and disposal of substrates produced by cells.

LSDs in many instances cause progressive physical and neurologic handicap. Several therapeutic strategies have been proposed so far to treat these diseases, but in most cases they have limitations, leave important issues unsolved and have a heavy impact on the quality of life of patients. We plan to test novel approaches, based on the use of drugs (so-called "small molecules") that may have advantages compared with existing therapies, such as a better distribution in the body and the possibility to be taken orally. We will test these new approaches in three of the most frequent LSDs, Pompe disease (PD), a severe and progressive muscle disease, Fabry disease (FD), a multisystem disease involving kidney, skin, heart and other organs, and mucopolysaccharidosis IIIA (MPSIIIA), a disease that causes progressive dementia. The strategies that we will use are aimed at enhancing the efficacy of enzyme replacement therapy, a therapeutic approach that is currently in use for several LSDs, or at reducing the rate of substrate synthesis and restoring the equilibrium between substrate synthesis and degradation.

Scientific publications

2015 ANNU REV MED
Lysosomal Storage Diseases: From Pathophysiology to Therapy
Parenti, G; Andria, G; Ballabio, A; Caskey, CTCites: 2 (*)
2014 MOLECULAR THERAPY
A Chaperone Enhances Blood alpha-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy
Parenti, G; Fecarotta, S; la Marce, G; Rossi, B; Ascione, S; Donati, MA; Morandis, LO; Ravaglia, S; Pichiecchio, A; Ombrone, D; Sacchini, M; Pasanisi, MB; De Filippi, P; Danesino, C; Della Casa, R; Romano, A; Mollica, C; Rosa, M; Agovino, T; Nusco, E; PorCites: 3 (*)
2014 FUTURE MED CHEM
Pharmacological chaperone therapy for lysosomal storage diseases
Parenti, G; Moracci, M; Fecarotta, S; Andria, GCites: 4 (*)
2013 EMBO MOLECULAR MEDICINE
Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease
Spampanato, C; Feeney, E; Li, LS; Cardone, M; Lim, JA; Annunziata, F; Zare, H; Polishchuk, R; Puertollano, R; Parenti, G; Ballabio, A; Raben, NCites: 34 (*)
2013 AUTOPHAGY
What else is in store for autophagy? Exocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease
Feeney, EJ; Spampanato, C; Puertollano, R; Ballabio, A; Parenti, G; Raben, NCites: 2 (*)
2012 JOURNAL OF INHERITED METABOLIC DISEASE
Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and the human recombinant alpha-galactosidase A in cultured fibroblasts from patients with Fabry disease
Porto, C;Pisani, A;Rosa, M;Acampora, E;Avolio, V;Tuzzi, MR;Visciano, B;Gagliardo, C;Materazzi, S;la Marca, G;Andria, G;Parenti, GCites: 19 (*)
2012 MOLECULAR GENETICS AND METABOLISM
Enzyme replacement therapy in patients with Fabry disease: State of the art and review of the literature
Pisani, A; Visciano, B; Roux, GD; Sabbatini, M; Porto, C; Parenti, G; Imbriaco, MCites: 17 (*)
2012 MOLECULAR THERAPY
Pharmacological Enhancement of alpha-Glucosidase by the Allosteric Chaperone N-acetylcysteine
Porto, C; Ferrara, MC; Meli, M; Acampora, E; Avolio, V; Rosa, M; Cobucci-Ponzano, B; Colombo, G; Moracci, M; Andria, G; Parenti, GCites: 18 (*)
2011 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
The Videofluoroscopic Swallowing Study Shows a Sustained Improvement of Dysphagia in Children With Niemann-Pick Disease Type C After Therapy With Miglustat
Fecarotta, S; Amitrano, M; Romano, A; Della Casa, R; Bruschini, D; Astarita, L; Parenti, G; Andria, GCites: 15 (*)
2011 HUMAN MUTATION
IDUA Mutational Profiling of a Cohort of 102 European Patients with Mucopolysaccharidosis Type I: Identification and Characterization of 35 Novel alpha-L-iduronidase (IDUA) Alleles
Bertola, F; Filocamo, M; Casati, G; Mort, M; Rosano, C; Tylki-Szymanska, A; Tuysuz, B; Gabrielli, O; Grossi, S; Scarpa, M; Parenti, G; Antuzzi, D; Dalmau, J; Di Rocco, M; Vici, CD; Okur, I; Rosell, J; Rovelli, A; Furlan, F; Rigoldi, M; Biondi, A; Cooper, Cites: 13 (*)
2011 CURRENT PHARMACEUTICAL BIOTECHNOLOGY
Pompe Disease: From New Views on Pathophysiology to Innovative Therapeutic Strategies
Parenti, G; Andria, GCites: 16 (*)