Workpackage 1

Pathogenesis and pathophysiology of lysosomal storage diseases

Leader of the WP is Andrea Ballabio from the Telethon Institute of Genetics and Medicine (Naples, Italy).

The general aim of WP1 is to study the mechanisms involved in cell damage and dysfunction (and thus leading to disease) in patients with lysosomal storage diseases (LSDs).

Recent studies have suggested that many factors play a role in the pathophysiology of LSDs. The accumulation of autophagic vacuoles, programmed cell death and chronic inflammation have been associated with the pathogenesis and progression of several lysosomal disorders. Understanding the biological mechanisms at the basis of these secondary effects and how they might relate to substrate storage has strong implications for the understanding of human LSD pathogenesis and possible implications for therapy.

To this end we will investigate three LSDs: Multiple Sulfatase Deficiency (MSD), Pompe disease, and MPS VI and in particular we will focus on:

1. Understanding the pathogenetic mechanisms underlying Multiple Sulfatase Deficiency (MSD) and type VI Mucopolysaccharidosis (MPS VI) in particular investigating the involvement of autophagy, cell death and inflammation.

2. Understanding the pathophysiology of Pompe disease (PD) by determining markers of disease stages, investigating the bases for the clinical diversity among patients and the role of autophagy in the course of the disease.