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

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number100101
Pages (from-to)1-6
Number of pages6
JournalBrain Disorders
Early online date3 Nov 2023
Publication statusPublished - 1 Dec 2023


  • Biomarker
  • Integrated stress response
  • NanoString
  • Vanishing white matter

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