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Basic and clinical research for clarify the pathophysiology and development of new terapeutic trial for Rett syndrome

Research Project

Project/Area Number 15K09608
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKurume University

Principal Investigator

Matsuishi Toyojiro  久留米大学, 付置研究所, 教授 (60157237)

Co-Investigator(Kenkyū-buntansha) 高橋 知之  久留米大学, 医学部, 准教授 (20332687)
御船 弘治  久留米大学, 医学部, 准教授 (70174117)
山下 裕史朗  久留米大学, 医学部, 教授 (90211630)
Research Collaborator Yuge Kotarou  久留米大学, 医学部, 助教 (20624472)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsRett症候群 / 発達障害 / 自閉症スペクトラム障害 / MECP2遺伝子 / STXBP1遺伝子 / HDAC8遺伝子 / 不整脈 / 肺炎 / レット症候群 / MECP2 / グレリン / ジストニア / 振戦 / トランスレーショナルリサーチ / 自閉症スペクトラム / 自律神経 / SHANK3遺伝子 / ES細胞 / iPS細胞 / モデル動物 / 心臓分化
Outline of Final Research Achievements

Rett syndrome (RTT) is a neurodevelopmental disorder, caused by MECP2 gene mutation. Patients showed dystonia, and tremor.We speculated that ghrelin may play an important role in RTT. We found that ghrelin markedly improved dystonia, tremor in 2 patients and constipation improved all 4 patients. We founded that RTT caused by a novel STXBP1 mutation, and also due to a mutation in HDAC8 gene.
Previous studies reported cardiac arrhythmias plays an important role in sudden death of RTT. We detected methylation of the CpG islands in the Tbx5 locus. Our results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure.
Respiratory infection is the most common cause of death in RTT. Our results indicated that aspiration might be a cause of Mecp2-null mice. MeCP2 deficiency affected the expression of several neuromodulator genes in the lower brainstem, especially SP is involved.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (55 results)

All 2017 2016 2015

All Journal Article (19 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 19 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (21 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results) Book (13 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Pathogenesis of Lethal Aspiration Pneumonia in Mecp2-null Mouse Model for Rett Syndrome.2017

    • Author(s)
      Hiroshi Kida, Tomoyuki Takahashi, Yuki Nakamura, Takashi Kinoshita, Munetsugu Hara, Masaki Okamoto, Satoko Okayama, Keiichiro Nakamura, Ken-ichiro Kosai, Takayuki Taniwaki, Yushiro Yamashita, Toyojiro Matsuishi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12293-12298

    • DOI

      10.1038/s41598-017-12293-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ghrelin improves dystonia and tremor in patients with Rett syndrome: A pilot study2017

    • Author(s)
      Yuge K, Hara M, Okabe R, Nakamura Y, Okamura H, Nagamitsu S, Yamashita Y, Orimoto K, Kojima M, Matsuishi T
    • Journal Title

      J Neurol Sci

      Volume: 377 Pages: 219-223

    • DOI

      10.1016/j.jns.2017.04.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased cortisol awakening response after completing the summer treatment program in children with ADHD.2017

    • Author(s)
      Okabe R, Okamura H, Egami C, Tada Y, Anai C, Mukasa A, Iemura A, Nagamitsu S, Furusho J, Matsuishi T, Yamashita Y.
    • Journal Title

      Brain Dev.

      Volume: S0387-7604 Issue: 7 Pages: 30035-9

    • DOI

      10.1016/j.braindev.2017.03.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Influence of sleep-onst time on the development of 18-monts-old infants: Japan Children’s cohort study2016

    • Author(s)
      Iemura A, Iwasaki M, Yamakawa N, Tomiwa K, Anji Y, Sakakihara Y, Kakuma T, Nagamitsu S, Matsuishi T
    • Journal Title

      Brain Dev

      Volume: 38 Pages: 364-372

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute encephalopathy with biphasic seizures and late reduced diffusion aasociated with staphylococcal toxic shock syndrome by burns2016

    • Author(s)
      Yokochi T, Sakanishi S, Ishidou Y, Kawano G, Matsuishi T, Akita Y, Obu K
    • Journal Title

      Brain Dev

      Volume: 38 Pages: 875-879

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Children’s eating atttitudes test: reliability and validation in Japanese adolescents2016

    • Author(s)
      Chiba H, Nagamitsu S, sakurai R, Mukai T, Shintou H, Yamasgita Y, Kakuma T, Uchimura N, Matsuishi T
    • Journal Title

      Eating Behaviors

      Volume: 23 Pages: 120-125

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Altered SPECT (123)I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa2016

    • Author(s)
      Nagamitsu S, Sakurai R, Matsuoka M et al.
    • Journal Title

      Front Psychiatry

      Volume: 7 Pages: 16-16

    • DOI

      10.3389/fpsyt.2016.00016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 典型的なけいれん重積型二相性脳症とは異なる経過でbright tree appearanceを呈した2症例2016

    • Author(s)
      横地賢興、竹内孝仁、向井純平、石堂雄毅、松石豊次郎、秋田幸大、大部敬三
    • Journal Title

      日本小児救急医学会誌

      Volume: 15 Pages: 61-65

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 小児の摂食障害における転帰評価因子の検討2016

    • Author(s)
      千葉比呂美、永光信一郎、櫻井利恵子、日吉佑介、松岡美智子、山下裕史朗、角間辰之、内村直尚、松石豊次郎
    • Journal Title

      子どもの心とからだ

      Volume: 25 Pages: 212-216

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] ADHD-like behavior in a patient with hypothalamic hamartoma2016

    • Author(s)
      Katayama K,Yamashita Y,Yatsuga S,Koga Y,Matsuishi
    • Journal Title

      Brain Dev

      Volume: 38 Issue: 1 Pages: 145-148

    • DOI

      10.1016/j.braindev.2015.05.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prediction of acute encephalopathy with biphasic seizures and late reduced diffusion in patients with febrile status epilepticus2015

    • Author(s)
      Yokochi T,Takeuchi T,Mukai J,Akita Y, Nagai K,Obu K,Kakuma T,Matsuishi T
    • Journal Title

      Brain Dev

      Volume: 38 Pages: 217-224

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Developmental trajectories for attention and working memory in healthy Japanese school-aged children2015

    • Author(s)
      Egami C,Yamashita Y,Tada Y,Anai C,Mukasa A,Yuge K,Nagamitsu S,Matsuishi T
    • Journal Title

      Brain Dev

      Volume: 37 Pages: 840-848

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Upregulated GABA inhibitory function in ADHD children with child behavior checklist-dysregulation profile:123I-iomazeni1 SPECT study2015

    • Author(s)
      Nagamitsu S,Yamashita Y,Tanigawa H,Chida H,Kaida H,Ishibashi M,Kakuma T,Croarkin PE,Matsuishi T
    • Journal Title

      Fronties in Psychistry

      Volume: 6 Pages: 1-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-nu11 mice to arrhythmias2015

    • Author(s)
      Hara M,Takahashi T,Mitsumasu C,Igata S,Takano M,Minami T,Yasukawa H,Okayama S,Nakamura K,Okabe Y,Tanaka E,Takemura G,Kosai K,Yamashita Y,Matsuishi T
    • Journal Title

      Cientific Reports

      Volume: 5 Pages: 11204-11204

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse.2015

    • Author(s)
      Tsuchiya Y., Minami Y., Umemura Y., Watanabe H., Ono D., Nakamura W., Takahashi T., Honma S., Kondoh G., Matsuishi T. & Yagita K.
    • Journal Title

      Genes to Cells

      Volume: 20 Issue: 12 Pages: 992-1005

    • DOI

      10.1111/gtc.12305

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ADHD 単独群とASD合併群のサマートリートメント・プログラムとペアレントトレーニングの効果2015

    • Author(s)
      免田 賢、向笠 章子、家村 明子、山下 裕史朗、松石 豊次郎
    • Journal Title

      小児の精神と神経

      Volume: 55 Pages: 25-38

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] ADHD 児のための家庭生活評価尺度の信頼性および妥当性の検証2015

    • Author(s)
      向笠 章子、山下 裕史朗、多田 泰裕、穴井 千鶴、江上 千代美、家村 明子、弓削 康太郎、松石 豊次郎
    • Journal Title

      久留米医学会雑誌

      Volume: 78 Pages: 162-168

    • NAID

      40020555744

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 小児科学の豊かな鉱脈と小児科医の社会貢献2015

    • Author(s)
      松石 豊次郎
    • Journal Title

      久留米医学会雑誌

      Volume: 78 Pages: 129-141

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient2015

    • Author(s)
      Hara M,Ohda C,Yamashita Y,Satsu H,Matsumoto N,Matsuishi T:
    • Journal Title

      Am J Med Genet A

      Volume: 167 Pages: 1593-1596

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of therapeutic strategies for Rett syndrome2017

    • Author(s)
      織本健司、松石豊次郎、弓削康太郎
    • Organizer
      ConBio 2017 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 言語能力保持型Rett症候群のGenotype-phenotype relationshipと治療反応性の分子制御機構2017

    • Author(s)
      Orimoto K, Matsuishi T, Yuge K
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathogenesis of lung injury in Mecp2-null mouse model for Rett syndrome2017

    • Author(s)
      4.Kida H, Takahashi T, Nakamura Y, Ninoshita T, Okayama S, Nakamura K, Kosai K, Taniwaki T, Yamashita Y, Matsuishi T
    • Organizer
      ConBio 2017 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 言語能力保持型レット症候群に対するアリプラゾールの言語情動機能改善効果―言語にとって情動とは何かー2017

    • Author(s)
      織本健司、松石豊次郎、弓削康太郎
    • Organizer
      第41回日本高次脳機能障害学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Japanese Rett Syndrome Database Consortium2016

    • Author(s)
      Itoh M, Saikusa T, Ikenaga T, Hirayama S, Nabatame S, Matsuishi T
    • Organizer
      RTT 50.1 The 50th Anniversary of the First Publication Wienon Rett Syndrome
    • Place of Presentation
      Wien, Austria
    • Year and Date
      2016-09-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経科学からみた発達障害2016

    • Author(s)
      松石豊次郎
    • Organizer
      第18回「子どもの心」研修科医
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 新生児~学童期の睡眠は発達障害予測の指標になるか?2016

    • Author(s)
      松石豊次郎
    • Organizer
      日本赤ちゃん学会 第16回学術集会
    • Place of Presentation
      京都
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Rett症候群の謎に挑戦する2016

    • Author(s)
      松石豊次郎
    • Organizer
      小児神経学クリニック 瀬川塾講演
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] レット症候群のグレリン治療について2016

    • Author(s)
      松石豊次郎、弓削康太郎、児島将康
    • Organizer
      小児神経学クリニック 瀬川塾講演
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Development of the therapeutic strategies for Rett syndrome2016

    • Author(s)
      Orimoto K, Matsuishi T, Yuge K
    • Organizer
      第39回日本分子生物学会総会
    • Place of Presentation
      横浜
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] バルプロ酸(VPA)投与後、遷延する嘔吐が軽快した錯乱型片頭痛の1例2016

    • Author(s)
      村美彩、三宅 淳、寺澤藍子、松下美由紀、中嶋洋介、横地賢興、岡本陽子、石本和久、工藤嘉公、河野 剛、秋田幸大、松石豊次郎、大部敬三
    • Organizer
      第484回日本小児科学会福岡地方会
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
  • [Presentation] Histone deacetylation 8(HDAC8)遺伝子変異により非典型的Rett 症候群をきたした女児の1 例2016

    • Author(s)
      七種朋子、下村 豪、弓削康太郎、原 宗嗣、永光信一郎、山下裕史朗、松石豊次郎、松本直道
    • Organizer
      第58回日本小児神経学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2016 Research-status Report
  • [Presentation] Children’s Eating Attitudes Test: Reliability and Validation in Japanese Adolecents2016

    • Author(s)
      Nagamitsu S, Chiba H, Sakurai R, Mukai T, Shintou H, Yamashita Y, Kakuma T, Matsuishi T
    • Organizer
      The 12th Asian Society for Pediatric Research (ASPR)
    • Place of Presentation
      Bangkok, Thai
    • Related Report
      2016 Research-status Report
  • [Presentation] 筑後地区における聖マリア病院小児神経の役割2016

    • Author(s)
      松石豊次郎
    • Organizer
      第3回聖マリア医師同門会総会特別講演
    • Place of Presentation
      久留米
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 代理人によるMunchausen症候群が疑われた1例2015

    • Author(s)
      坂本藍子、児玉麻亜子、三宅淳、田中玄師、松下美由紀、喜多村美幸、中嶋洋介、岡本陽子、石本和久、秋田幸大、大部敬三、松石豊次郎
    • Organizer
      第66回聖マリア医学会
    • Place of Presentation
      久留米市
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Study of Rstt syndrome epidemiology and database in Japan2015

    • Author(s)
      Itoh M, Mabatame S,Tachimori H.Matsuishi T
    • Organizer
      4th European Congress on Rett Syndrome
    • Place of Presentation
      Roma, Italia
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多臓器に症状を呈し、発達遅延、てんかんのある4カ月男児2015

    • Author(s)
      島さほ、寺澤藍子、下村豪、弓削康太郎、永光信一郎、山下裕史朗、松石豊次郎
    • Organizer
      第79回日本小児神経学会九州地方会
    • Place of Presentation
      北九州市
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 発達障害の大切な知識―バイオマーカーと睡眠ー2015

    • Author(s)
      松石豊次郎
    • Organizer
      平成27年浮羽乳幼児保健会
    • Place of Presentation
      浮羽市
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 発達障害を考える―神経科学、睡眠の立場から―2015

    • Author(s)
      松石豊次郎
    • Organizer
      八女筑後地区学校保健会
    • Place of Presentation
      八女市
    • Year and Date
      2015-06-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] グレリンはレット症候群の症状を改善するか?―レット症候群に対する新規治療開発の検討―2015

    • Author(s)
      弓削康太郎、七種朋子、平田留美子、中村祐樹、岡村尚昌、原宗嗣、大矢崇志、永光 信一郎、山下 裕史朗、児島 将康、伊藤 雅之、松石 豊次郎
    • Organizer
      第57回日本小児神経学会学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 小児神経学からみた発達障害―自験例、研究を踏まえて―2015

    • Author(s)
      松石豊次郎
    • Organizer
      Lilly ADHD 全国学術講演会
    • Place of Presentation
      福岡市
    • Year and Date
      2015-04-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] 1-16.Rett症候群.稀少てんかん診療指針.第2章 疾患の特徴と診療指針 1. てんかん症候群、日本てんかん学会(編集)2017

    • Author(s)
      松石豊次郎
    • Publisher
      診断と治療社
    • Related Report
      2017 Annual Research Report
  • [Book] 21.レット症候群.てんかんの指定難病ガイド、厚生労働省科学研究 補助金 難治性疾患政策研究事業「希少難病てんかんのレジストリ構築による総合的研 究」班2017

    • Author(s)
      松石豊次郎
    • Publisher
      日興美術株式会社
    • Related Report
      2017 Annual Research Report
  • [Book] 時間の風景920 出会いのありがたさと忘れられない患者さん2017

    • Author(s)
      松石豊次郎
    • Total Pages
      22
    • Publisher
      Medical Tribune
    • Related Report
      2016 Research-status Report
  • [Book] 慢性疾患児の一生を診る.・神経疾患 Rett症候群2016

    • Author(s)
      松石豊次郎
    • Publisher
      小児内科
    • Related Report
      2016 Research-status Report
  • [Book] 稀少てんかんの診療指標.第2章 疾患の特徴と診療指標 1-16 Rett症候群2016

    • Author(s)
      松石豊次郎
    • Publisher
      診断と治療社
    • Related Report
      2016 Research-status Report
  • [Book] Ⅱ.主要徴喉 D.意識障害、小児救急治療ガイドライン 第3版2015

    • Author(s)
      河野剛、松石豊次郎
    • Publisher
      診断と治療社
    • Related Report
      2015 Research-status Report
  • [Book] 知的障害、小児脳神経外科学改訂第2版、12章 脳神経外科医が知っておくべき各領域の知識。小児神経内科領域2015

    • Author(s)
      松石豊次郎
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report
  • [Book] 自閉症スペクトラム症(障害)、小児神経外科学改訂第2版、12章 脳神経外科医が知っておくべき各領域の知識。小児神経内科領域、2015

    • Author(s)
      松石豊次郎
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report
  • [Book] 注意欠如/多動症(障害)、小児神経外科学改訂第2版、12章 脳神経外科医が知っておくべき各領域の知識。小児神経内科領域、2015

    • Author(s)
      松石豊次郎
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report
  • [Book] 小児の頭痛、小児脳神経外科学改定第2版、12章 脳神経外科医が知っておくべき各領域の知識。小児神経内科領域、2015

    • Author(s)
      松石豊次郎
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report
  • [Book] 発達性協調運動障害、小児脳神経外科学改定第2版、12章 脳神経外科医が知っておくべき各領域の知識。小児神経内科領域2015

    • Author(s)
      松石豊次郎
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report
  • [Book] レット症候群の概要 ①1レット症候群の歴史 レット症候群 診療ガイドブック2015

    • Author(s)
      松石豊次郎
    • Publisher
      大阪大学出版会
    • Related Report
      2015 Research-status Report
  • [Book] レット症候群の概要 2.よくある症状の解説と対処法.16.思春期・第二次性徴、内分泌 レット症候群 診療ガイドブック2015

    • Author(s)
      松石豊次郎
    • Publisher
      大阪大学出版会
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 外国特許出願申請2017

    • Inventor(s)
      松石豊次郎、児島将康、弓削康太郎、原宗嗣、山下裕史朗
    • Industrial Property Rights Holder
      松石豊次郎、児島将康、弓削康太郎、原宗嗣、山下裕史朗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-202751
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] グレリンを有効成分として含有するレット症候群(RTT)の予防・治療2016

    • Inventor(s)
      松石豊次郎、弓削康太郎、児島将康、原宗嗣、山下裕史朗
    • Industrial Property Rights Holder
      松石豊次郎、弓削康太郎、児島将康、原宗嗣、山下裕史朗
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-04-14
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2019-12-27  

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