Evidence map›Paper›PMID 19587708›Full record

ArticleGene therapy2009

Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the neurological disease progression in MPS IIIB mice.

D M McCarty, J DiRosario, K Gulaid, J Muenzer, H Fu

Open access · greenAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  17. Review
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 1 country.

D M McCartyThe Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43205, USA.
J DiRosario
K Gulaid
J Muenzer
H Fu
The Ohio State University · USNationwide Children's Hospital · USUniversity of North Carolina at Chapel Hill · US

Funding

CNS Gene Therapy for Mucopolysaccharidosis IIIB w/ AAVR01DK063972 · NIDDK · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI FU, HAIYAN · 2002 to 2004
$742k
NIDDK NIH HHS R01 DK063972NIDDK NIH HHS R01 DK63972
6 · The paper itself

Abstract

The presence of the blood-brain barrier (BBB) presents the most critical challenge in therapeutic development for mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological manifestation, because of alpha-N-acetylglucosaminidase (NaGlu) deficiency. Earlier, we showed a global central nervous system (CNS) transduction in mice by mannitol-facilitated entry of intravenous (IV)-delivered recombinant adeno-associated viral serotype 2 (rAAV2) vector. In this study, we optimized the approach and showed that the maximal transduction in the CNS occurred when the rAAV2 vector was IV injected at 8 min after mannitol administration, and was approximately 10-fold more efficient than IV delivery of the vector at 5 or 10 min after mannitol infusion. Using this optimal (8 min) regimen, a single IV infusion of rAAV2-CMV-hNaGlu vector is therapeutically beneficial for treating the CNS disease of MPS IIIB in adult mice, with significantly extended survival, improved behavioral performance, and reduction of brain lysosomal storage pathology. The therapeutic benefit correlated with maximal delivery to the CNS, but not peripheral tissues. This milestone data shows the first effective gene delivery across the BBB to treat CNS disease. The critical timing of vector delivery and mannitol infusion highlights the important contribution of this pretreatment to successful intervention, and the long history of safe use of mannitol in patients bodes well for its application in CNS gene therapy.

Indexed as

AcetylglucosaminidaseAnimalsBlood-Brain BarrierDependovirusDisease ProgressionGenetic VectorsMannitolMaze LearningMiceMice, Inbred C57BLMice, KnockoutMucopolysaccharidosis IIIRecombinant ProteinsSurvival AnalysisTissue DistributionTransduction, GeneticAcetylglucosaminidasealpha-N-acetyl-D-glucosaminidaseMannitolRecombinant Proteins

Identifiers

PMID19587708
PMCPMC4289609
OpenAlexW1978350886

What OpenQuestion holds

Textmetadata
LicenceTDM
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.