Evidence map›Paper›PMID 38429928›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

Chun Hang Lau, Maral J Rouhani, Elizabeth F Maughan, Jessica C Orr, Krishna K Kolluri, David R Pearce, Elizabeth K Haughey, Liam Sutton, Sam Flatau, Pablo Lopez Balboa and 10 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
2.6field-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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Skin Development and Disease: A Molecular Perspective.Current issues in molecular biology · 2024
    Review
  5. Of LAMA3 and LAMB3: A novel gene therapy for epidermolysis bullosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

Chun Hang LauEpithelial Cell Biology in ENT Research (EpiCENTR) Group, UCL Great Ormond Street Institute of Child Health, University College London, 20c Guilford Street, London WC1N 1DZ, UK.
Maral J RouhaniLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK; Ear, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Elizabeth F MaughanEpithelial Cell Biology in ENT Research (EpiCENTR) Group, UCL Great Ormond Street Institute of Child Health, University College London, 20c Guilford Street, London WC1N 1DZ, UK; Ear, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Jessica C OrrEpithelial Cell Biology in ENT Research (EpiCENTR) Group, UCL Great Ormond Street Institute of Child Health, University College London, 20c Guilford Street, London WC1N 1DZ, UK; Lungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
Krishna K KolluriLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
David R PearceUCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
Elizabeth K HaugheyInfection, Immunity, and Inflammation Department, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Liam SuttonEar, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Sam FlatauEar, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Pablo Lopez BalboaDepartment of Dermatology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Maria Laura BagetaDepartment of Dermatology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Christopher O'CallaghanInfection, Immunity, and Inflammation Department, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Claire M SmithInfection, Immunity, and Inflammation Department, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Sam M JanesLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
Richard HewittEar, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Gabriela PetrofDepartment of Dermatology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Anna E MartinezDepartment of Dermatology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
John A McGrathSt John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, St Thomas Street, London SE1 9RT, UK.
Colin R ButlerEpithelial Cell Biology in ENT Research (EpiCENTR) Group, UCL Great Ormond Street Institute of Child Health, University College London, 20c Guilford Street, London WC1N 1DZ, UK; Ear, Nose, and Throat Department, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK. Electronic address: colin.butler@ucl.ac.uk.
Robert E HyndsEpithelial Cell Biology in ENT Research (EpiCENTR) Group, UCL Great Ormond Street Institute of Child Health, University College London, 20c Guilford Street, London WC1N 1DZ, UK; UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK. Electronic address: rob.hynds@ucl.ac.uk.
Great Ormond Street Hospital for Children NHS Foundation Trust · GBUniversity College London · GBGreat Ormond Street Hospital · GBGuy's Hospital · GB

Funding

Medical Research Council MR/R015635/1Medical Research Council MR/W025051/1Wellcome TrustWellcome Trust WT209199/Z/17/Z
6 · The paper itself

Abstract

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Indexed as

Cell AdhesionEpidermolysis BullosaLamininLentivirusAdolescentCells, CulturedChildChild, PreschoolEpithelial CellsFemaleGene ExpressionGenetic TherapyGenetic VectorsHumansInfantMaleLamininlaminin alpha 3airway basal cellscell adhesionepidermolysis bullosaextracellular matrixin vitro cell culturelaminin-332larynxlentiviral transductiontrachea

Identifiers

PMID38429928
PMCPMC11081864
OpenAlexW4392284329

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.