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i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1<sup>G93A</sup> mice.

Overview

Authors: Noriyuki Watanabe1,2,3, Yumi Kawahori1,2, Vinh Ta1, Dongsheng Wang1,2, Kenneth A. Ohgi1,2, Hongxia Wang1,2, Natalia Kleschevnikova1,2, Eiichi Ishikawa3, Brian P. Head1,2
ORCID iDs: Noriyuki Watanabe, Brian P. Head
  1. Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA
  2. VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
  3. Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1- Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Institutions: University of Tsukuba (Japan); University of California San Diego (United States); VA San Diego Healthcare System (United States)
Journal: Molecular therapy. Advances, volume 34, issue 3, article 201820
Dates: received 5 February 2026; accepted 26 July 2026; published online 27 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.omta.2026.201820 · PMID 42614372 · PMCID PMC13481751 · OpenAlex W7171373121
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: mouse (organism), other condition (population)
Methods: Spectral & time-frequency, Statistics, fMRI & imaging, Physiology & signal measures
Keywords: AAV9-SynCav1, intracerebroventricular administration, amyotrophic lateral sclerosis, caveolin-1, motor neuron, neuroprotection
Topic: Caveolin-1 and cellular processes (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: VA RCS (BX006318); Congressionally Directed Medical Research Programs (CDMRP) (AL210059); ALSTIA (AL230115); ALSTDA; UCSD (2039592)
Citations: not cited yet (Europe PMC); 44 references in the paper

Abstract

Practical and broad biodistributable gene delivery interventions are essential for advancing therapeutic strategies targeting neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We previously demonstrated that subpial delivery of AAV9-synapsin-promoted caveolin-1 (SynCav1) afforded significant neuroprotective effects in mutant superoxide dismutase (SOD)-1-induced ALS pathology. However, subpial delivery is regionally restricted, technically challenging, and highly invasive. This study evaluated whether the intracerebroventricular (i.c.v.) route of administration (ROA), an alternative CNS delivery strategy less invasive than direct spinal cord injections, could achieve broader CNS biodistribution and produce functional or histological benefits in hSOD1G93A mice. i.c.v. administration of AAV9-SynCav1 achieved widespread Cav-1 overexpression in the motor cortex and spinal cord. SynCav1-treated male mice exhibited improved running wheel (RW) performance and better motor-evoked potentials. Immunofluorescence revealed attenuated degeneration of cholinergic motor neurons (MNs) in the cervical and lumbar ventral horn, as well as preserved diaphragm neuromuscular junction (NMJ) innervation in SynCav1-treated mice. These findings serve as preclinical proof of concept that i.c.v. delivery of AAV9-SynCav1 can achieve CNS target engagement and produce selective functional and anatomical benefits in hSOD1G93A mice.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data and code availability

The data that support findings of this study are available within this study or available from the corresponding author (B.P.H.) upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added Noriyuki Watanabe (0000-0001-5941-3369); Brian P. Head (0000-0001-9417-5351); removed Noriyuki Watanabe; Brian P. Head

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 5 funders, 44 references.

Cite

This paper

Watanabe, N., Kawahori, Y., Ta, V., Wang, D., Ohgi, K. A., Wang, H., Kleschevnikova, N., Ishikawa, E., & Head, B. P. (2026). i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1<sup>G93A</sup> mice. Molecular therapy. Advances, 34(3), 201820. https://doi.org/10.1016/j.omta.2026.201820

BibTeX

@article{watanabe2026i,
author = {Watanabe, Noriyuki and Kawahori, Yumi and Ta, Vinh and Wang, Dongsheng and Ohgi, Kenneth A. and Wang, Hongxia and Kleschevnikova, Natalia and Ishikawa, Eiichi and Head, Brian P.},
title = {{i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1\<sup\>G93A\</sup\> mice}},
journal = {Molecular therapy. Advances},
year = {2026},
month = jul,
volume = {34},
number = {3},
pages = {201820},
publisher = {American Society of Gene \& Cell Therapy},
issn = {3117-387X},
doi = {10.1016/j.omta.2026.201820},
url = {https://doi.org/10.1016/j.omta.2026.201820},
pmid = {42614372},
pmcid = {PMC13481751}
}

RIS

TY - JOUR
AU - Watanabe, Noriyuki
AU - Kawahori, Yumi
AU - Ta, Vinh
AU - Wang, Dongsheng
AU - Ohgi, Kenneth A.
AU - Wang, Hongxia
AU - Kleschevnikova, Natalia
AU - Ishikawa, Eiichi
AU - Head, Brian P.
TI - i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1<sup>G93A</sup> mice
T2 - Molecular therapy. Advances
J2 - Mol Ther Adv
PY - 2026
DA - 2026/07/27
VL - 34
IS - 3
SP - 201820
SN - 3117-387X
PB - American Society of Gene & Cell Therapy
DO - 10.1016/j.omta.2026.201820
UR - https://doi.org/10.1016/j.omta.2026.201820
LA - en
ER -

CSL-JSON

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