Evidence map›Paper›PMID 25273354›Full record

ArticleGene therapy2014

Gene therapy approach to FAP: in vivo influence of T119M in TTR deposition in a transgenic V30M mouse model.

A R Batista, D Gianni, M Ventosa, A V Coelho, M R Almeida, M Sena-Esteves, M J Saraiva

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Biophysical characterization and modulation of Transthyretin Ala97Ser.Annals of clinical and translational neurology · 2019
    Article
  4. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

A R Batista1] Molecular Neurobiology, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal [2] Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
D GianniDepartment of Neurology, Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
M VentosaInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
A V CoelhoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
M R Almeida1] Molecular Neurobiology, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal [2] Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
M Sena-EstevesDepartment of Neurology, Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
M J Saraiva1] Molecular Neurobiology, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal [2] Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
Universidade do Porto · PTUniversidade Nova de Lisboa · PTUniversity of Massachusetts Chan Medical School · USInstituto de Biologia Molecular e Celular

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.

Indexed as

Amyloid Neuropathies, FamilialAnimalsDependovirusDisease Models, AnimalElectrophoresis, Gel, Two-DimensionalEndoplasmic Reticulum StressExtracellular Matrix ProteinsGene Expression RegulationGenetic MarkersGenetic TherapyGenetic VectorsGene Transfer TechniquesLiverMatrix Metalloproteinase 9MiceMice, TransgenicExtracellular Matrix ProteinsGenetic MarkersMatrix Metalloproteinase 9Mmp9 protein, mousePrealbumin

Identifiers

PMID25273354
OpenAlexW2008689268

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.