RT Journal Article
T1 The New Pharmacological Chaperones PBXs Increase alpha-Galactosidase A Activity in Fabry Disease Cellular Models
A1 Besada, Pedro
A1 Gallardo-Gomez, Maria
A1 Perez-Marquez, Tania
A1 Patino-alvarez, Lucia
A1 Pantano, Sergio
A1 Silva-Lopez, Carlos
A1 Teran, Carmen
A1 Arevalo-Gomez, Ana
A1 Ruz-Zafra, Aurora
A1 Fernandez-Martin, Julian
A1 Ortolano, Saida
K1 Fabry disease
K1 pharmacological chaperones
K1 GLA variants
K1 Migalastat
K1 lysosomal storage diseases
K1 Therapy
K1 Defect
AB Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal alpha-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize alpha-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of alpha-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of alpha-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.
PB Mdpi
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/24783
UL https://hdl.handle.net/10668/24783
LA en
DS RISalud
RD Apr 6, 2025