Enzyme replacement therapy for Fabry disease: possible strate-gies to improve its efficacy

ABSTRACT: Enzyme Replacement Therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, it has many limitations, in terms of costs, high rh-protein re-quired, and side effects; thus, its optimization would be beneficial for patients. In this paper, we describe preliminary results paving the way for two possible approaches: i. combination of en-zyme replacement therapy with pharmacological chaperones; ii. identification of approved drugs that affect the AGAL interactors' expression. We show that galactose, a low-affinity phar-macological chaperone, can prolong rh-AGAL half-life in FD cells. We compared the wild-type AGAL and the rh-AGAL interactomes and identified a list of drugs known to affect them. This list represents a starting point to deeply screen approved drugs and identify those that can bene-fit the enzyme replacement therapy and those that can negatively interfere with it.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Fabry Disease

SUBMITTER: Flora Cozzolino  

LAB HEAD: Prof.ssa Maria Monti

PROVIDER: PXD039168 | Pride | 2023-05-10

REPOSITORIES: Pride