Surrogate Cerebrospinal Fluid Biomarkers for Assessing the Efficacy of Gene Therapy in Hurler Syndrome - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 Accéder directement au contenu
Article Dans Une Revue Frontiers in Neurology Année : 2021

Surrogate Cerebrospinal Fluid Biomarkers for Assessing the Efficacy of Gene Therapy in Hurler Syndrome

Résumé

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal hydroxylase alpha- l -iduronidase (IDUA). The resulting accumulation of dermatan and heparan sulfate induces intellectual disabilities and pre-mature death, and only a few treatment options are available. In a previous study, we demonstrated the feasibility, safety, and efficacy of gene therapy by injecting recombinant adeno-associated viral vector serotype (AAV)2/5-IDUA into the brain of a canine model of MPS I. We report on a quantitative proteomic analysis of control dogs and untreated dogs with MPS I cerebrospinal fluid (CSF) that had been collected throughout the study in the MPS I dogs. Mass spectrometry (MS) analysis identified numerous proteins present at altered levels in MPS I CSF samples. Quantitative immunoblotting, performed on CSF from healthy controls, untreated MPS I dogs, and MPS I dogs early treated and late treated by gene therapy, confirmed the MS data for a subset of proteins with higher abundance (neuronal pentraxin 1, chitinase 3-like 1, monocyte differentiation antigen CD14, and insulin-like growth factor-binding protein 2). Scoring of the results shows that the expression levels of these proteins are close to those of the control group for dogs that underwent gene therapy early in life but not for older treated animals. Our results disclose four novel predictive biomarker candidates that might be valuable in monitoring the course of the neurological disease in MPS patients at diagnosis, during clinical follow-up, and after treatment.
Fichier principal
Vignette du fichier
Reiner_2021.pdf (391.47 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03665889 , version 1 (12-05-2022)

Licence

Paternité

Identifiants

Citer

Reiner Haseloff, Stéphanie Trudel, Ramona Birke, Michael Schümann, Eberhard Krause, et al.. Surrogate Cerebrospinal Fluid Biomarkers for Assessing the Efficacy of Gene Therapy in Hurler Syndrome. Frontiers in Neurology, 2021, 12, pp.640547. ⟨10.3389/fneur.2021.640547⟩. ⟨hal-03665889⟩
34 Consultations
22 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More