Evidence map›Paper›PMID 42281208›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Cerebrospinal delivery of a bidirectional AAV9 vector improves optic nerve and retinal pathology in a sheep model of Tay-Sachs disease.

Brett D Story, Sara M Thomasy, Sara A Adelman, Toloo Taghian, Yvette Lopez, Monica Ardon, Hikaru Shiraishi, Sabina Khan, Meher Khan, Maria Do and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Brett D StoryDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA. Electronic address: storydvm@gmail.com.
Sara M ThomasyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA; Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA 95817, USA.
Sara A AdelmanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Toloo TaghianDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Yvette LopezDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Monica ArdonDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Hikaru ShiraishiDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Sabina KhanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Meher KhanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Maria DoDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Hector R BenattiDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Stephanie BertrandTufts Farm, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.
Rachel PrestigiacomoDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Rachael GatelyDepartment of Ambulatory and Theriogenology, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.
Douglas R MartinScott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Auburn, AL 36849, USA.
Miguel Sena-EstevesDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jun XieDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Guangping GaoDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Leandro B C TeixeiraDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Gillian C ShawDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Nicholas Marsh-ArmstrongDepartment of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA 95817, USA.
Heather L Gray-EdwardsDepartment of Genetic and Cellular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Funding

VISION RESEARCH CORE GRANTP30EY012576 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI MARIE E BURNS · 1999 to 2026
$18.9M
Diversity Supplement: Advancing novel therapies for optic neuropathy with a nonhuman primate modelR01EY033733 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Sara Michelle Thomasy · 2023 to 2026
$2.9M
Global AAV gene therapy of Tay-Sachs disease in sheep.K08NS096219 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GRAY-EDWARDS, HEATHER L · 2017 to 2021
$906k
NEI NIH HHS P30 EY012576NEI NIH HHS R01 EY033733NINDS NIH HHS K08 NS096219
6 · The paper itself

Abstract

Tay-Sachs disease (TSD) is a fatal neurodegenerative lysosomal storage disease. The Jacob sheep is the only large-animal model of TSD, yet ocular pathology and the therapeutic potential of gene therapy remain poorly defined. Sheep cohorts included normal controls (n = 3); untreated TSD-affected (n = 4); intravenous AAV9-Bic_HexA/HexB-treated (n = 3); and intracerebroventricular, cisterna magna, and lumbar intrathecal AAV9- Bic_HexA/HexB-treated sheep (cerebrospinal fluid [CSF] therapy; n = 7). Retinal histopathology and immunohistochemistry, retinal whole-mount analyses for retinal ganglion cell (RGC) morphology and density, optic nerve evaluation with p-phenylenediamine (PPD )semi-thin sections, qPCR assessment for vector genomes, and RNAscope probes for transgene expression were performed. Untreated TSD sheep exhibited RGCs with abundant microvesicular cytoplasmic expansion and optic nerve spheroids, with storage material variably staining with periodic acid-Schiff. Marked astrocytosis, microgliosis, and GM2 accumulation within RGCs were present. Optic nerve axon counts and RGC density were significantly reduced, and optic nerve damage scores increased, in untreated and IV-treated sheep but were rescued with short-term CSF therapy. GM2 volume and signal intensity per RGC were significantly reduced following short-term CSF therapy. Minimal but detectable retinal vector genomes and transgene expression were observed. These findings demonstrate retinal and optic nerve pathology in Jacob sheep with TSD and AAV9 therapy.

Indexed as

DependovirusGenetic TherapyGenetic VectorsOptic NerveRetinaTay-Sachs DiseaseAnimalsDisease Models, AnimalGene Therapy AgentsRetinal Ganglion CellsSheepTransgenesdevelopmentgene therapylysosomesneurological disorderstherapeutics

Identifiers

PMID42281208
PMCPMC13508168

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.