mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.

Journal

Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086

Informations de publication

Date de publication:
10 Jan 2024
Historique:
medline: 10 1 2024
pubmed: 10 1 2024
entrez: 10 1 2024
Statut: ppublish

Résumé

The urea cycle enzyme argininosuccinate lyase (ASL) enables the clearance of neurotoxic ammonia and the biosynthesis of arginine. Patients with ASL deficiency present with argininosuccinic aciduria, an inherited metabolic disease with hyperammonemia and a systemic phenotype coinciding with neurocognitive impairment and chronic liver disease. Here, we describe the dysregulation of glutathione biosynthesis and upstream cysteine utilization in ASL-deficient patients and mice using targeted metabolomics and in vivo positron emission tomography (PET) imaging using (

Identifiants

DOI: 10.1126/scitranslmed.adh1334 PMID: 38198573
pubmed: 38198573
doi: 10.1126/scitranslmed.adh1334
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eadh1334

Auteurs

Sonam Gurung (S)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0003-3271-5273

Oskar Vilhelmsson Timmermand (OV)

School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
ORCID: 0000-0002-4187-1588

Dany Perocheau (D)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0001-5450-8801

Ana Luisa Gil-Martinez (AL)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0001-8455-5676

Magdalena Minnion (M)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.

Loukia Touramanidou (L)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.

Sherry Fang (S)

Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

Martina Messina (M)

Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
ORCID: 0000-0003-0466-0922

Youssef Khalil (Y)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0001-9025-3017

Justyna Spiewak (J)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.

Abigail R Barber (AR)

School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
ORCID: 0009-0008-0238-2686

Richard S Edwards (RS)

School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
ORCID: 0000-0002-9178-7691

Patricia Lipari Pinto (PL)

Santa Maria's Hospital, Lisbon North University Hospital Center, 1649-028 Lisbon, Portugal.
ORCID: 0000-0001-9197-7586

Patrick F Finn (PF)

Moderna Inc., Cambridge, MA 02139, USA.
ORCID: 0000-0003-1333-5400

Alex Cavedon (A)

Moderna Inc., Cambridge, MA 02139, USA.
ORCID: 0009-0009-1226-5704

Summar Siddiqui (S)

Moderna Inc., Cambridge, MA 02139, USA.

Lisa Rice (L)

Moderna Inc., Cambridge, MA 02139, USA.

Paolo G V Martini (PGV)

Moderna Inc., Cambridge, MA 02139, USA.
ORCID: 0000-0002-0051-797X

Deborah Ridout (D)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0003-1336-6450

Wendy Heywood (W)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.

Ian Hargreaves (I)

Pharmacy and Biomolecular Sciences, Liverpool John Moore University, Liverpool L3 5UG, UK.

Simon Heales (S)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
ORCID: 0000-0002-9906-0200

Philippa B Mills (PB)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.

Simon N Waddington (SN)

EGA Institute for Women's Health, University College London, London WC1E 6HX, UK.
Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of Witswatersrand, Braamfontein, 2000 Johannesburg, South Africa.
ORCID: 0000-0003-4970-4730

Paul Gissen (P)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
National Institute of Health Research Great Ormond Street Biomedical Research Centre, London WC1N 1EH, UK.
ORCID: 0000-0002-9712-6122

Simon Eaton (S)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0003-0892-9204

Mina Ryten (M)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
ORCID: 0000-0001-9520-6957

Martin Feelisch (M)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
ORCID: 0000-0003-2320-1158

Andrea Frassetto (A)

Moderna Inc., Cambridge, MA 02139, USA.

Timothy H Witney (TH)

School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
ORCID: 0000-0002-9475-2873

Julien Baruteau (J)

Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
National Institute of Health Research Great Ormond Street Biomedical Research Centre, London WC1N 1EH, UK.
ORCID: 0000-0003-0582-540X

Classifications MeSH