Autophagy induction as a novel therapeutic strategy for MSD

The lysosomal degradation pathway of autophagy has a crucial role in different pathophysiological conditions, such as infection, neurodegenerative disorders, cancer and ageing. In particular, autophagy plays an important role in the pathophysiology of a family of inborn errors of metabolism due to defect in the activity of lysosomal enzymes, known as Lysosomal Storage Disorders (LSDs). Thus, strategies for modulation of autophagy may represent a fascinating therapeutic prospective for treating this class of disorders. Most lysosomal storage diseases are caused by deficiencies of single lysosomal enzyme, while in Multiple Sulfatase Deficiency (MSD), a rare autosomal recessive disorder, the activities of all lysosomal enzyme ?sulfatases? are profoundly impaired due to mutations in the SUMF1 (Sulfatase Modifying Factor 1) gene. SUMF1 activity is an essential limiting step for the conversion of a conserved cysteine into a formylglycine residue: this post-translation modification is required to confer to sulfatases their catalytic activity. Recently we have generated a new hypomorphic mouse model of the Multiple Sulfatase Deficiency (MSD) that better reproduces the pathological features observed in patients. The goal of this study is to test the efficacy of a novel therapeutic strategy for MSD, based on a pharmacological approach, which is the administration of TAT-Beclin1 peptide, a potent in vivo modulator of autophagy, in the new hypomorphic mouse model.

Award Date
28 June 2018
Award Value
Principal Investigator
Professor Andrea Ballabio
Host Institution
Fondazione Telethon
MRCG-HRB Joint Funding Scheme