TY - JOUR
T1 - ISR mRNAs as potential blood biomarkers in patients with vanishing white matter
AU - Oudejans, Ellen
AU - Rooijen-van Leeuwen, Gemma van
AU - Takanohashi, Asako
AU - van der Sluis, Sophie
AU - Abbink, Truus E. M.
AU - Vanderver, Adeline L.
AU - van der Knaap, Marjo S.
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Integrated stress response
KW - NanoString
KW - Vanishing white matter
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U2 - https://doi.org/10.1016/j.dscb.2023.100101
DO - https://doi.org/10.1016/j.dscb.2023.100101
M3 - Article
SN - 2666-4593
VL - 12
SP - 1
EP - 6
JO - Brain Disorders
JF - Brain Disorders
M1 - 100101
ER -