Development of transcutaneous immunization system for Alzheimer's disease

• Project/Area Number: 24790154
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kinki University
• Principal Investigator: MATSUO Kazuhiko 近畿大学, 薬学部, 助教 (70615921)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: アルツハイマー型認知症 / 経皮ワクチン / 自己溶解型マイクロニードル / アルツハイマー病

Research Abstract

Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treatment of AD. Injectable immunization of amyloid beta peptide (Ab) as antigens showed therapeutic efficacy; therefore, a clinical trial was conducted. However, the clinical trial was stopped due to the incidence of meningoencephalitis caused by excess activation of Th1 cells infiltrating the brain as a serious adverse reaction. Because recent studies have suggested that transcutaneous immunization (TCI) is likely to elicit Th2-dominant immune responses, in this study, we investigated the vaccine efficacy of TCI against AD using a novel dissolving microneedle array (MicroHyala; MH). Our TCI induced anti-Ab1-42 immune responses by simple and low-invasive application of Ab-containing MH to the skin. Unfortunately, this TCI resulted in little significant improvement in cognitive function and Th2-dominant immune responses, suggesting the need for further modification.

Research Products

• [Journal Article] Vaccine efficacy of transcutaneous immunization with amyloidβusing a dissolving microneedle array in a mouse model of Alzheimer's disease (2014)
  • Author(s): Matsuo K, Okamoto H, Kawai Y, Quan YS, Kamiyama F, Hirobe S, Okada N, Nakagawa S
  • Journal Title: J. Neuroimmunol Volume: 266 Pages: 1-11
• [Journal Article] Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease (2014)
  • Author(s): Matsuo K, Okamoto H, Kawai Y, Quan YS, Kamiyama F, Hirobe S, Okada N, Nakagawa S
  • Journal Title: Journal of Neuroimmunology Volume: 266 Issue: 1-2 Pages: 1-11
  • DOI: 10.1016/j.jneuroim.2013.11.002
  • Peer Reviewed
• [Journal Article] A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedles patch for soluble and particulate antige ns (2012)
  • Author(s): Kazuhiko Matsuo, Yayoi Yokota, You Zhai, Ying Shu Quan, Fumio Kamiyama, Yohei Mukai, Naoki Okada, and Shinsaku Nakagawa
  • Journal Title: Journal of Controlled Release Volume: 161 Issue: 1 Pages: 10-17
  • DOI: 10.1016/j.jconrel.2012.01.033
  • Peer Reviewed
• [Journal Article] Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza (2012)
  • Author(s): Matsuo K, Hirobe S, Yokota Y, Ayabe Y, Seto M, Quan YS, Kamiyama F, Tougan T, Horii T, Mukai Y, Okada N, Nakagawa S
  • Journal Title: J Control Release Volume: 160(3) Issue: 3 Pages: 495-501
  • DOI: 10.1016/j.jconrel.2012.04.001
  • Peer Reviewed