Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes

Srinivasarao Repudi, Irina Kustanovich, Sara Abu-Swai, Shani Stern, View ORCID ProfileRami I. Aqeilan
doi: https://doi.org/10.1101/2021.04.27.441575
Srinivasarao Repudi
1The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irina Kustanovich
2Sagol Department of Neurobiology, University of Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sara Abu-Swai
1The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shani Stern
2Sagol Department of Neurobiology, University of Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rami I. Aqeilan
1The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rami I. Aqeilan
  • For correspondence: ramiaq@mail.huji.ac.il
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

WW domain-containing oxidoreductase (WWOX) is an emerging neural gene regulating homeostasis of the central nervous system. Germline biallelic mutations in WWOX cause WWOX-related epileptic encephalopathy (WOREE) syndrome and spinocerebellar ataxia, and autosomal recessive 12 (SCAR12), two devastating neurodevelopmental disorders with highly heterogenous clinical outcomes, the most common being severe epileptic encephalopathy and profound global developmental delay. We recently demonstrated that neuronal ablation of murine Wwox recapitulates phenotypes of Wwox-null mice leading to intractable epilepsy, hypomyelination and postnatal lethality. Here, we designed and produced an adeno-associated viral vector harboring murine Wwox or human WWOX cDNA and driven by the human neuronal Synapsin I promoter (AAV-SynI-WWOX). Testing the efficacy of AAV-SynI-WWOX delivery in Wwox null mice demonstrated that specific neuronal restoration of WWOX expression rescued brain hyperexcitability and seizures, hypoglycemia, and myelination deficits as well as the premature lethality of Wwox-null mice. These findings provide a proof-of-concept for WWOX gene therapy as a promising approach to curing children with WOREE and SCAR12.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted April 27, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes
Srinivasarao Repudi, Irina Kustanovich, Sara Abu-Swai, Shani Stern, Rami I. Aqeilan
bioRxiv 2021.04.27.441575; doi: https://doi.org/10.1101/2021.04.27.441575
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes
Srinivasarao Repudi, Irina Kustanovich, Sara Abu-Swai, Shani Stern, Rami I. Aqeilan
bioRxiv 2021.04.27.441575; doi: https://doi.org/10.1101/2021.04.27.441575

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13248)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47368)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)