MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.

AAV gene therapy Mecp2 Pitt Hopkins syndrome TCF4

Journal

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381

Informations de publication

Date de publication:
14 Jun 2024
Historique:
received: 17 10 2023
revised: 07 05 2024
accepted: 14 05 2024
medline: 15 6 2024
pubmed: 15 6 2024
entrez: 14 6 2024
Statut: aheadofprint

Résumé

The neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett syndrome (RTT) patients. However, RTT is caused by MECP2 mutations whereas mutations in the TCF4 gene lead to PTHS. The mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists. We reprogrammed patient skin derived fibroblasts into induced neuronal progenitor cells. Interestingly, we discovered that MeCP2 levels were decreased in PTHS patient iNPCs relative to healthy controls and that both iNPCs and iAstrocytes displayed defects in function and differentiation in a mutation-specific manner. When Tcf4

Identifiants

DOI: 10.1016/j.neurot.2024.e00376 PMID: 38876822
pubmed: 38876822
pii: S1878-7479(24)00062-X
doi: 10.1016/j.neurot.2024.e00376
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e00376

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kathrin C Meyer, Patricia Cogram, Colleen M. Niswender reports financial support was provided by Pitt Hopkins Research Foundation. Colleen M. Niswender reports was provided by International Rett Syndrome Foundation. Rocco G. Gogliotti, Sheryl Anne D. Vermudez reports financial support was provided by National Institutes of Health. Kathrin Meyer, Cassandra Dennys has patent pending to Nationwide Children's Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Cassandra N Dennys (CN)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Sheryl Anne D Vermudez (SAD)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA.

Robert J M Deacon (RJM)

Department of Genetics, Institute of Ecology and Biodiversity, Faculty of Science, University of Chile, Chile.

J Andrea Sierra-Delgado (JA)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Kelly Rich (K)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Xiaojin Zhang (X)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Aditi Buch (A)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA.

Kelly Weiss (K)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA.

Yuta Moxley (Y)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA.

Hemangi Rajpal (H)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA.

Francisca D Espinoza (FD)

Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, 4090541, Chile.

Samantha Powers (S)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Ariel S Ávila (AS)

Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, 4090541, Chile.

Rocco G Gogliotti (RG)

Department of Molecular Pharmacology and Neuroscience, Loyola University Chicago, Maywood, IL 60153, USA.

Patricia Cogram (P)

Department of Genetics, Institute of Ecology and Biodiversity, Faculty of Science, University of Chile, Chile.

Colleen M Niswender (CM)

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Kathrin C Meyer (KC)

Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Medical Center, Columbus, OH, USA; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: km2dq@missouri.edu.

Classifications MeSH