Journal of Genetic Syndromes & Gene Therapy
Open Access

Exploiting new therapeutic strategies for treating lysosome storage disorders

5^th Annual Congress on Rare Diseases and Orphan Drugs

August 29-30, 2018 | Boston, USA

Alessandro Luciani

University of Zurich, Switzerland

Posters & Accepted Abstracts: J Genet Syndr Gene Ther

Abstract :

Lysosomes are small organelles containing enzymes able to digest many different molecules in the cell, thus regulating cell homeostasis. Rare genetic diseases involving the lysosomes lead to accumulation of undigested material in the cells, often reflected by severe, multi-organ complications. Cystinosis is a lysosomal storage disease characterized by dysfunction of proximal tubular epithelial cells, resulting in massive losses of vital solutes in the urine. The mechanisms linking lysosomal defect and epithelial dysfunction remain unknown, preventing the development of disease-modifying therapies. We recently reported that lysosomal alterations in cystinosis lead to defective autophagic clearance of mitochondria and increased oxidative stress which in turn, activates the transcription factor ZOâ??1associated Yâ??box factor ZONAB impairing cell differentiation, hence epithelial transport and function. We have also demonstrated that correction of the primary lysosomal defect, neutralization of mitochondrial oxidative stress, and blockage of tight junction-associated ZONAB signaling, they rescue epithelial function in cystinosis cells. Our findings suggest a heretofore unknown cascade that links congenital defects in lysosomes and life-threatening kidney disease, providing new therapeutic perspectives for treating cystinosis and lysosomal storage disorders.

Biography :

E-mail: alessandro.luciani@uzh.ch