Research on treatment of Parkinson's disease utilizing optogenetics and iPS cell

• Project/Area Number: 15K19498
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: OYAMA GENKO 順天堂大学, 医学部, 准教授 (00407256)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: iPS / dopamine / controllable / optogenetics / ドパミン / パーキンソン病 / 光遺伝学 / iPS細胞 / ドパミン神経

Outline of Final Research Achievements

Fetal cell transplantation for Parkinson's disease did not become a general treatment due to off dyskinesia or tumor formation. Although it is expected to solve the problem by transplanting cells derived from induced pluripotent stem (iPS) cells, its safety and effect are uncertain. In this study, to overcome these problems, we aimed to develop a controllable iPS cell induced dopamine neuron transplantation therapy. Channelrhodopsin 2 was transfected in to iPS cell derived dopamine neuron with Lenti virus. The controllable dopamine neuron was transplanted into striatum of 6-hydroxydopamine dyskinesia model mouse. We confirmed the transplanted cells engrafted without tumorigenesis in the mouse brain and differentiated into dopamine neurons.

Research Products

• [Journal Article] Deep Brain Stimulation for Parkinson Disease:Mechanisms and New Technology (2017)
  • Author(s): 梅村淳，下泰司，岩室宏一，大山彦光，服部信孝，新井一
  • Journal Title: Neurological Surgery 脳神経外科 Volume: 45 Issue: 1 Pages: 5-14
  • DOI: 10.11477/mf.1436203439
  • ISSN: 0301-2603, 1882-1251
  • Year and Date: 2017-01-10
• [Journal Article] A novel mutation of CHCHD2 p.R8H in a sporadic case of Parkinson's disease (2017)
  • Author(s): Ikeda, Aya; Matsushima, Takashi; Daida, Kensuke; Nakajima, Sho; Conedera, Silvio; Li, Yuanzhe; Yoshino, Hiroyo; Oyama, Genko; Funayama, Manabu; Nishioka, Kenya; Hattori, Nobutaka
  • Journal Title: PARKINSONISM & RELATED DISORDERS Volume: 34 Pages: 66-68
  • DOI: 10.1016/j.parkreldis.2016.10.018
  • Peer Reviewed
• [Journal Article] Management of impulse control disorders with deep brain stimulation: A double-edged sword. (2017)
  • Author(s): Kasemsuk C, Oyama G, Hattori N.
  • Journal Title: J Neurol Sci. Volume: 374 Pages: 63-68
  • DOI: 10.1016/j.jns.2017.01.019
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Current Topics in Deep Brain Stimulation for Parkinson Disease. (2016)
  • Author(s): Umemura A, Oyama G, Shimo Y, Nakajima M, Nakajima A, Jo T, Sekimoto S, Ito M, Mitsuhashi T, Hattori N, Arai H.
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 56 Pages: 613-625
• [Journal Article] A randomized double-blind multi-center trial of hydrogen water for Parkinson’s disease: protocol and baseline characteristics (2016)
  • Author(s): Yoritaka, A.,Abe, T.,Ohtsuka, C.,Maeda, T., Hirayama, M. et al
  • Journal Title: BMC Neurology Volume: 16 Issue: 1 Pages: 66-66
  • DOI: 10.1186/s12883-016-0589-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of zonisamide on post-traumatic Holmes’ tremor. (2016)
  • Author(s): Sekimoto S, Oyama G, Izawa N, Ueno S, Jo T, Shimo Y, Nakajima A, Nakajima M, Umemura A, Arai H, Hattori N
  • Journal Title: Neurol Clin Neurosci Volume: 4 Issue: 5 Pages: 184-185
  • DOI: 10.1111/ncn3.12063
  • Peer Reviewed / Open Access
• [Journal Article] Interleaving stimulation with a combination of bipolar and monopolar configurations for secondary failure of bilateral subthalamic stimulation in Parkinson's disease (2016)
  • Author(s): Tsukada R, Oyama G, Shimo Y, Sekimoto S, Jo T, Nakajima A, Umemura A, Arai H, Hattori
  • Journal Title: Neurology and Clinical Neuroscience Volume: 5 Issue: 1 Pages: 32-33
  • DOI: 10.1111/ncn3.12085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Atypical parkinsonism caused by Pro105Leu mutation of prion protein: A broad clinical spectrum. (2016)
  • Author(s): Mano KK, Matsukawa T, Mitsui J, Ishiura H, Tokushige S, Takahashi Y, Sato NS, Nakamoto FK, Ichikawa Y, Nagashima Y, Terao Y, Shimizu J, Hamada M, Uesaka Y, Oyama G, Ogawa G, Yoshimura J, Doi K, Morishita S, Tsuji S, Goto J.
  • Journal Title: Neurol Genet. Volume: 2 Issue: 1 Pages: 1-9
  • DOI: 10.1212/nxg.0000000000000048
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism. (2015)
  • Author(s): Nishioka K, Oyama G, Yoshino H, Li Y, Matsushima T, Takeuchi C, Mochizuki Y, Mori-Yoshimura M, Murata M, Yamasita C, Nakamura N, Konishi Y, Ohi K, Ichikawa K, Terada T, Obi T, Funayama M, Saiki S, Hattori N.
  • Journal Title: Neurobiol Aging. Volume: S0197 Issue: 5 Pages: 54-58
  • DOI: 10.1016/j.neurobiolaging.2015.01.020
  • Peer Reviewed
• [Journal Article] Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance-Adams syndrome. (2015)
  • Author(s): Asahi T, Kashiwazaki D, Dougu N, Oyama G, Takashima S, Tanaka K, Kuroda S.
  • Journal Title: J Neurol. Volume: 262 Issue: 6 Pages: 1581-1583
  • DOI: 10.1007/s00415-015-7748-x
  • Peer Reviewed
• [Presentation] Transplantation therapy of human iPS cell-derived dopamine neural progenitor cells for Parkinson’s disease (2018)
  • Author(s): Ryota Nakamura, Genko Oyama, Takayuki Jo, Kei-ichi Ishikawa, Risa Nonaka, Yasushi Shimo, Wado Akamatsu, Nobutaka Hattori
  • Organizer: International Congress of Parkinson’s Disease and Movement Disorders
  • Int'l Joint Research
• [Presentation] Perils and pitfalls of neuromodulation in Parkinson’s disease (2016)
  • Author(s): Genko Oyama, Yasushi Shimo, Atsushi Umemura, Nobutaka Hattori
  • Organizer: 5th Asian Oceanian Parkinson's Disease and Movement Disorders Congress
  • Place of Presentation: Manila, Philippines
  • Year and Date: 2016-11-11
  • Int'l Joint Research / Invited
• [Presentation] Uncommon application of DBSin movement disorders (2016)
  • Author(s): Genko Oyama, Yasushi Shimo, Atsushi Umemura, Nobutaka Hattori
  • Organizer: The 1st Korean International Movement Disorders Conference
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2016-10-28
  • Int'l Joint Research / Invited
• [Presentation] Update on Deep Brain Stimulation for Parkinson’s Disease and Other Movement Disorders (2016)
  • Author(s): Genko Oyama, Yasushi Shimo, Atsushi Umemura, Nobutaka Hattori
  • Organizer: the Basic Scientists Summer School of Movement Disorder Society Asian and Oceanian Section
  • Place of Presentation: Suzhou, China
  • Year and Date: 2016-08-04
  • Int'l Joint Research / Invited
• [Presentation] Fast-scan cyclic voltammetryによるiPS細胞由来 ドパミン神経細胞のドパミン放出機能検出法の確立 (2016)
  • Author(s): 大山彦光, 城崇之, 石川景一, 赤松和土, 服部信孝
  • Organizer: カテコールアミンと 神経疾患研究会2016
  • Place of Presentation: 東京
• [Presentation] Optical neuromodulation of nigrostriatal pathway (2015)
  • Author(s): Takayuki Jo, Genko Oyama, Kenji Yoshimi, Shigeto Sato, Teruko Danjo, Atsushi Umemura, Yasushi Shimo, Nobutaka Hattori
  • Organizer: 19th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-06-14
  • Int'l Joint Research
• [Presentation] Optogenetic Neuromodulation (2015)
  • Author(s): Genko Oyama, Jo Takashi, Kenji Yoshimi, Nobutaka Hattori
  • Organizer: the 67th American Academy of Neurology Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research