Oxidative stress biomarkers in Fabry disease: is there a room for them?
Biomarkers
Fabry disease
Oxidative stress
lysoGb3
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
22
04
2020
accepted:
01
07
2020
revised:
14
06
2020
pubmed:
29
7
2020
medline:
22
6
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels. Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.
Sections du résumé
BACKGROUND
BACKGROUND
Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression.
METHODS
METHODS
We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls.
RESULTS
RESULTS
AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels.
CONCLUSIONS
CONCLUSIONS
Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.
Identifiants
pubmed: 32719972
doi: 10.1007/s00415-020-10044-w
pii: 10.1007/s00415-020-10044-w
pmc: PMC7674365
doi:
Substances chimiques
Biomarkers
0
alpha-Galactosidase
EC 3.2.1.22
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3741-3752Subventions
Organisme : Partially supported by an Investigator-Initiated Research grant from Shire International GmbH, a Takeda company.
ID : IIR-ITA-001466
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