ISR mRNAs as potential blood biomarkers in patients with vanishing white matter

Ellen Oudejans; Gemma van Rooijen-van Leeuwen; Asako Takanohashi; Sophie van der Sluis; Truus E.M. Abbink; Adeline L. Vanderver; Marjo S. van der Knaap

Brain Disorders (Dec 2023)

ISR mRNAs as potential blood biomarkers in patients with vanishing white matter

Ellen Oudejans,
Gemma van Rooijen-van Leeuwen,
Asako Takanohashi,
Sophie van der Sluis,
Truus E.M. Abbink,
Adeline L. Vanderver,
Marjo S. van der Knaap

Affiliations

Ellen Oudejans: Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
Gemma van Rooijen-van Leeuwen: Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
Asako Takanohashi: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States
Sophie van der Sluis: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, the Netherlands; Department of Child and Adolescence Psychiatry, section Complex Trait Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Truus E.M. Abbink: Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
Adeline L. Vanderver: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Department of Neurology, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Marjo S. van der Knaap: Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Corresponding author.

Journal volume & issue: Vol. 12
p. 100101

Abstract

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Vanishing white matter (VWM) is a leukodystrophy caused by bi-allelic pathogenic variants in the eukaryotic initiation factor 2B (eIF2B). eIF2B orchestrates the integrated stress response (ISR), a physiological response to cellular stress. In VWM brain, the ISR is deregulated. The degree of ISR deregulation has been shown to correlate positively with disease severity in a representative VWM mouse model. Preclinical studies have shown that the ISR is a viable treatment target for VWM. Suitable biomarkers to assess disease activity and ISR-target engagement in patients are lacking. Therefore, the current study aimed to find potential blood mRNA biomarkers for VWM with nanoString technology. The technology confirmed ISR deregulation in the brains of VWM patients but did not identify a single ISR blood biomarker that can be readily used in clinical setting. A set of three mRNAs that are differentially expressed in blood between VWM patients and controls was detected.

Published in Brain Disorders

ISSN: 2666-4593 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.journals.elsevier.com/brain-disorders

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