Biomedicines (Sep 2024)

Comprehensive High-Depth Proteomic Analysis of Plasma Extracellular Vesicles Containing Preparations in Rett Syndrome

  • Sho Hagiwara,
  • Tadashi Shiohama,
  • Satoru Takahashi,
  • Masaki Ishikawa,
  • Yusuke Kawashima,
  • Hironori Sato,
  • Daisuke Sawada,
  • Tomoko Uchida,
  • Hideki Uchikawa,
  • Hironobu Kobayashi,
  • Megumi Shiota,
  • Shin Nabatame,
  • Keita Tsujimura,
  • Hiromichi Hamada,
  • Keiichiro Suzuki

DOI
https://doi.org/10.3390/biomedicines12102172
Journal volume & issue
Vol. 12, no. 10
p. 2172

Abstract

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Backgroud: Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents. Methods: In this study, we performed a high-depth proteomic analysis of extracellular vesicles containing preparations extracted from patient plasma samples to identify novel biomarkers. Results: We identified 33 upregulated and 17 downregulated candidate proteins among a total of 4273 proteins in RTT compared to the healthy controls. Among these, UBE3B was predominantly increased in patients with Rett syndrome and exhibited a strong correlation with the clinical severity score, indicating the severity of the disease. Conclusions: We demonstrated that the proteomics of high-depth extracellular vesicles containing preparations in rare diseases could be valuable in identifying new disease biomarkers and understanding their pathophysiology.

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