Evidence map›Paper›PMID 32592687›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice.

Hannah G Lahey, Chelsea J Webber, Diane Golebiowski, Cassandra M Izzo, Erin Horn, Toloo Taghian, Paola Rodriguez, Ana Rita Batista, Lauren E Ellis, Misako Hwang and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. Trial
  2. Article
  3. Viral gene replication enhances AAV vector quality and reduces manufacturing costs.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  4. Review
  5. Article
  6. CRISPR-mediated targeting of theMolecular therapy. Advances · 2026
    Article
  7. Article
  8. Virotherapy as Gene Deliver for Anti-Cancer Therapy: A Review Article.Asian Pacific journal of cancer prevention : APJCP · 2025
    Review
  9. Review
  10. A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Therapeutic Strategies For Tay-Sachs Disease.Frontiers in pharmacology · 2022
    Review
  16. Article
  17. Review
  18. Viral vector platforms within the gene therapy landscape.Signal transduction and targeted therapy · 2021
    Review
  19. Letter to the Editor.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Hannah G LaheyDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Chelsea J WebberDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Diane GolebiowskiDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Cassandra M IzzoDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Erin HornDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Toloo TaghianDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Paola RodriguezDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Ana Rita BatistaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Lauren E EllisScott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Auburn, AL, USA.
Misako HwangScott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Auburn, AL, USA.
Douglas R MartinScott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Auburn, AL, USA; Department of Anatomy, Physiology & Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA.
Heather Gray-EdwardsDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Miguel Sena-EstevesDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: miguel.esteves@umassmed.edu.
University of Massachusetts Chan Medical School · USAuburn University · US

Funding

Whole-body therapy for GM2 gangliosidosesR01NS093941 · NINDS · AUBURN UNIVERSITY AT AUBURN · PI ESTEVES, MIGUEL S, MARTIN, DOUGLAS R · 2016 to 2020
$2.9M
NINDS NIH HHS R01 NS093941
6 · The paper itself

Abstract

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme β-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. The blood-brain barrier crossing properties of AAV9 enables systemic gene therapy; however, the requirement of co-delivery of two monocistronic AAV vectors to overexpress the heterodimeric HexA protein has prevented the use of this approach. To address this need, we developed multiple AAV constructs encoding simultaneously HEXA and HEXB using AAV9 and AAV-PHP.B and tested their therapeutic efficacy in 4- to 6-week-old SD mice after systemic administration. Survival and biochemical outcomes revealed superiority of the AAV vector design using a bidirectional CBA promoter with equivalent dose-dependent outcomes for both capsids. AAV-treated mice performed normally in tests of motor function, CNS GM2 ganglioside levels were significantly reduced, and survival increased by >4-fold with some animals surviving past 2 years of age.

Indexed as

Genetic TherapyAnimalsbeta-N-AcetylhexosaminidasesDependovirusDisease ManagementDisease Models, AnimalGene ExpressionGenetic Predisposition to DiseaseGenetic VectorsG(M2) GangliosideMiceMutationSandhoff DiseaseTay-Sachs DiseaseTransgenesbeta-N-AcetylhexosaminidasesG(M2) GangliosideAAV9gene therapyGM2 gangliosidosisintravenous deliverySandhoff diseaseTay-Sachs disease

Identifiers

PMID32592687
PMCPMC7544971
OpenAlexW3036008681

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.