Biomarker reserch for moyamoya disease in cerebrospinal fluid

• Project/Area Number: 24592121
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nagoya University
• Principal Investigator: OKAMOTO Sho 名古屋大学, 医学部附属病院, 講師 (10378036)
• Co-Investigator(Renkei-kenkyūsha): YOSHIKAWA Kazuhiro 愛知医科大学, 高度研究機器部門, 特任教授 (60109759)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: バイオマーカー / もやもや病 / プロテオミクス解析 / moyamoya disease / SELDI-TOF-MS / PENK

Outline of Final Research Achievements

We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid（CSF) in moyamoya disease(MMD) patients and the age dependent decrease of m/z 4473 peptide, and correlation between m/z 4473 peptide and postoperative angiogenesis were also suggested.
These peptides were revealed to be a proenkephalin 143-183. We quantified the concentration of proenkephalin 143-183 in the samples using sandwich ELISA. It was significantly higher in MMD (median 8,270pmol/L) than in control(median 3,760pmol/L)(P<0.001), and decreased as age dependent manner in MMD(r=-0.57; P<0.001). The AUC of the ROC curve in children (age<18 y.o) was 0.085 (95%CI, 0.741-1). A proenkephalin 143-183 in CSF may be a promising diagnostic biomarker, especially in pediatric MMD patients.
The etiology of MMD is unknown, but the effect of enkephalin peptides through opioid growth factor receptor or delta opioid receptor might be associated with the pathophysiology of MMD.

Research Products

• [Journal Article] Biomarker Research for Moyamoya Disease in Cerebrospinal Fluid Using Surface-enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry. (2015)
  • Author(s): Mikio Maruwaka, Kazuhiro Yoshikawa, Sho Okamoto, Yoshio Araki, Masaki Sumitomo, Akino Kawamura, Kinya Yokoyama, Toshihiko Wakabayashi
  • Journal Title: J Stroke Cerebrovasc Volume: 24 Pages: 104-111
  • Peer Reviewed
• [Journal Article] Biomarker Research for Moyamoya Disease in Cerebrospinal Fluid Using Surface-enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry (2015)
  • Author(s): Mikio Maruwaka, MD, Kazuhiro Yoshikawa, PhD, Sho Okamoto, PhD,Yoshio Araki, PhD, Masaki Sumitomo, MD, Akino Kawamura, MD,Kinya Yokoyama, MD,and Toshihiko Wakabayashi, PhD
  • Journal Title: Journal of stroke and cerebrovascular diseases Volume: in press
  • Peer Reviewed / Open Access
• [Presentation] もやもや病患者における髄液中での神経 ペプチドの上昇と病態生理についての考察 (2015)
  • Author(s): 横山 欣也, 岡本 奨, 圓若 幹夫, 清水 賢三, 坂本 悠介, 宇田 憲司, 太田 慎次,和田 健太郎, 村岡 真輔, 荒木 芳生,吉川 和宏, 若林 俊彦
  • Organizer: 第74回日本脳神経外科学会総会
  • Place of Presentation: 北海道 札幌市 ロイトン札幌
  • Year and Date: 2015-10-14
• [Presentation] もやもや病患者における髄液中での神経 ペプチドの上昇と病態生理についての考察 (2015)
  • Author(s): 横山 欣也, 岡本 奨, 圓若 幹夫, 清水 賢三, 坂本 悠介, 宇田 憲司, 太田 慎次,和田 健太郎, 村岡 真輔, 荒木 芳生,吉川 和宏, 若林 俊彦
  • Organizer: 第16回日本分子脳神経外科学会
  • Place of Presentation: 静岡県 浜松市 アクトシティ浜松
  • Year and Date: 2015-08-28
• [Presentation] SELDI-TOF MSを用いた小児と成人もやもや病患者の髄掖検体におけるバイオマーカーの研究 (2013)
  • Author(s): 横山欣也、岡本 奨
  • Organizer: 日本脳神経外科学会第72回学術総会
  • Place of Presentation: パシフィコ横浜 横浜市