Evidence map›Paper›PMID 24938696›Full record

ArticleThe Laryngoscope2014

Optimizing atoh1-induced vestibular hair cell regeneration.

Hinrich Staecker, Christina Schlecker, Shannon Kraft, Mark Praetorius, Chi Hsu, Douglas E Brough

Open access · greenAbstract read
In one paragraph

Article in The Laryngoscope, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Cochlear Gene Therapy.Cold Spring Harbor perspectives in medicine · 2019
    Review
  7. Toward the Optical Cochlear Implant.Cold Spring Harbor perspectives in medicine · 2019
    Review
  8. Article
  9. Emerging Gene Therapies for Genetic Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2017
    Review
  10. Article
  11. Review
  12. Article
  13. Article
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

6 authors at 3 institutions in 2 countries.

Hinrich StaeckerDepartment of Otolaryngology, Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas.
Christina Schlecker
Shannon Kraft
Mark Praetorius
Chi Hsu
Douglas E Brough
University of Kansas · USThe University of Kansas Health System · USHeidelberg University · DE

Funding

Development of atonal therapy for bilateral vestibular hypofunctionR01DC008424 · NIDCD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI STAECKER, HINRICH · 2007 to 2011
$2.0M
NIDCD NIH HHS R01 DC 008424NIDCD NIH HHS R01 DC008424
6 · The paper itself

Abstract

objectives/hypothesisDetermine the optimal design characteristics of an adenoviral (Ad) vector to deliver atoh1 and induce regeneration of vestibular hair cells. STUDY

designEvaluation of a mouse model of intralabyrinthine gene delivery. Tissue culture of mouse and human macular organs.

methodsMacular organs from adult C57Bl/6 mice were treated with binding modified and alternate adenovectors expressing green fluorescent protein (gfp) or luciferase (L). Expression of marker genes was determined over time to determine vector transfection efficiency. The inner ear of adult mice was then injected with modified vectors. Expression of gfp and distribution of vector DNA was followed. Hearing and balance function was evaluated in normal animals to ensure safety of the novel vector designs. An optimized vector was identified and tested for its ability to induce hair cell regeneration in a mouse vestibulopathy model. Finally, this vector was tested for its ability to induce hair cell regeneration in human tissue.

resultsAd5 serotype-based vectors were identified as having a variety of different binding capacities for inner ear tissue. This makes it difficult to limit the dose of vector due to entry into nontargeted cells. Screening of rare adenovector serotypes demonstrated that Ad-based vectors were ideally suited for delivery to supporting cells; therefore, they were useful for hair cell regeneration studies. Utilization of an Ad28-based vector to deliver atoh1 to a mouse model of vestibular loss resulted in significant functional recovery of balance. This vector was also capable of transfecting human macular organs and inducing regeneration of human vestibular hair cells in vitro.

conclusionsImprovement in vector design can lead to more specific cell-based delivery and reduction of nonspecific delivery of the trans gene, leading to the development of optimized molecular therapeutics to induce hair cell regeneration. LEVEL OF EVIDENCE: N/A. Laryngoscope 124:S1-S12, 2014.

Indexed as

Analysis of VarianceAnimalsBasic Helix-Loop-Helix ProteinsDisease Models, AnimalGenetic TherapyGenetic VectorsGene Transfer TechniquesHair Cells, VestibularHumansMiceMice, Inbred C57BLPolymerase Chain ReactionPostural BalanceRandom AllocationReal-Time Polymerase Chain ReactionRegenerationATOH1 protein, humanBasic Helix-Loop-Helix ProteinsadenovectorAtoh1balancehair cell regenerationviral vector

Identifiers

PMID24938696
PMCPMC5267505
OpenAlexW1846455627

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.