Evidence map›Paper›PMID 26447927›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII.

Brittney L Gurda, Adrien De Guilhem De Lataillade, Peter Bell, Yanqing Zhu, Hongwei Yu, Ping Wang, Jessica Bagel, Charles H Vite, Tracey Sikora, Christian Hinderer and 10 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Quantitative clinical characteristics of 53 patients with MPS VII: a cross-sectional analysis.Genetics in medicine : official journal of the American College of Medical Genetics · 2017
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art.International journal of molecular sciences · 2021
    Review
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

20 authors at 5 institutions in 2 countries.

Brittney L GurdaDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: bgurda@vet.upenn.edu.
Adrien De Guilhem De LatailladeUniversity of Nantes Medical School, Nantes, France.
Peter BellGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Yanqing ZhuGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Hongwei YuGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Ping WangDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jessica BagelDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Charles H ViteDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tracey SikoraDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Christian HindererGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Roberto CalcedoGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Alexander D YoxDepartment of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
Richard A SteetDepartment of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
Therese RuaneDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Patricia O'DonnellDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Guangping GaoGene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Microbiology and Physiology Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
James M WilsonGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Margret CasalDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Katherine P PonderDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Mark E HaskinsDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
University of Pennsylvania · USUniversity of Georgia · USNantes Université · FRUniversity of Massachusetts Chan Medical School · USWashington University in St. Louis · US

Funding

Vector CoreP30DK047757 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WILSON, JAMES M · 1993 to 2017
$18.0M
Referral Ctr-Animal models of human genetic diseaseP40OD010939 · OD · UNIVERSITY OF PENNSYLVANIA · PI CASAL, MARGRET L · 2012 to 2023
$7.9M
X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN THE DOGP40RR002512 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI HASKINS, MARK E · 1985 to 2011
$7.6M
Gene Therapy of Mucopolysaccharidosis VIIR01DK054481 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI CASAL, MARGRET L · 1998 to 2017
$7.0M
PATHOGENIC MECHANISMS OF LYSOSOMAL DISEASER01GM086524 · NIGMS · UNIVERSITY OF GEORGIA · PI STEET, RICHARD · 2009 to 2021
$4.0M
NCRR NIH HHS P40 RR002512NIDDK NIH HHS DK54481NIDDK NIH HHS P30 DK047757NIDDK NIH HHS P30DK047757NIDDK NIH HHS R01 DK054481NIGMS NIH HHS R01 GM086524NIH HHS OD P40-010939NIH HHS P40 OD010939
6 · The paper itself

Abstract

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease arising from mutations in β-d-glucuronidase (GUSB), which results in glycosaminoglycan (GAG) accumulation and a variety of clinical manifestations including neurological disease. Herein, MPS VII dogs were injected intravenously (i.v.) and/or intrathecally (i.t.) via the cisterna magna with AAV9 or AAVrh10 vectors carrying the canine GUSB cDNA. Although i.v. injection alone at 3 days of age resulted in normal cerebrospinal fluid (CSF) GUSB activity, brain tissue homogenates had only ~1 to 6% normal GUSB activity and continued to have elevated GAG storage. In contrast, i.t. injection at 3 weeks of age resulted in CSF GUSB activity 44-fold normal while brain tissue homogenates had >100% normal GUSB activity and reduced GAGs compared with untreated dogs. Markers for secondary storage and inflammation were eliminated in i.t.-treated dogs and reduced in i.v.-treated dogs compared with untreated dogs. Given that i.t.-treated dogs expressed higher levels of GUSB in the CNS tissues compared to those treated i.v., we conclude that i.t. injection of AAV9 or AAVrh10 vectors is more effective than i.v. injection alone in the large animal model of MPS VII.

Indexed as

AnimalsAnimals, NewbornCentral Nervous System DiseasesDependovirusDisease Models, AnimalDogsGenetic TherapyGenetic VectorsGlucuronidaseGlycosaminoglycansInjections, IntravenousInjections, SpinalMaleMucopolysaccharidosis VIIGlucuronidaseGlycosaminoglycans

Identifiers

PMID26447927
PMCPMC4817811
OpenAlexW2228780390

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.