Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome.
Acetylglucosaminidase
/ genetics
Child
Cytokines
/ metabolism
Drug Administration Routes
Genetic Therapy
/ adverse effects
Genetic Vectors
/ administration & dosage
Humans
Immunity, Cellular
Immunologic Memory
Lymphocyte Activation
Mucopolysaccharidosis III
/ complications
T-Lymphocytes
/ immunology
Transgenes
/ genetics
AAV
CNS
MPS IIIB
NAGLU
T cells
cellular immunity
cytokines
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
18
01
2021
accepted:
21
04
2021
entrez:
27
5
2021
pubmed:
28
5
2021
medline:
30
9
2021
Statut:
epublish
Résumé
Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. It was reported that AAV-mediated gene therapies might elicit a strong host immune response resulting in decreased transgene expression. To address this issue, we performed a comprehensive analysis of cellular immunity and cytokine patterns generated against the therapeutic enzyme in the four treated children over 5.5 years of follow-up. We report the emergence of memory and polyfunctional CD4
Identifiants
pubmed: 34040605
doi: 10.3389/fimmu.2021.655478
pmc: PMC8141743
doi:
Substances chimiques
Cytokines
0
alpha-N-acetyl-D-glucosaminidase
EC 3.2.1.50
Acetylglucosaminidase
EC 3.2.1.52
Banques de données
ClinicalTrials.gov
['NCT03300453']
ISRCTN
['ISRCTN19853672']
EudraCT
['2012-000856-33']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
655478Informations de copyright
Copyright © 2021 Gougeon, Poirier-Beaudouin, Ausseil, Zérah, Artaud, Heard, Deiva and Tardieu.
Déclaration de conflit d'intérêts
MT has received consulting fees from UniQure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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