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Development of treatment for autism spectrum disorder relating with oxytocin and miRNA

Research Project

Project/Area Number 19K08258
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionJichi Medical University

Principal Investigator

Yamagata Takanori  自治医科大学, 医学部, 客員教授 (00239857)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自閉スペクトラム症 / オキシトシン / MECP2重複症候群 / Rett症候群 / miRNA / AAV9 / MECP2 / 遺伝子治療 / 神経発達症 / MECP2関連疾患 / 概日リズム関連遺伝子 / 治療
Outline of Research at the Start

自閉スペクトラム症(ASD)の治療法開発を、オキシトシン神経系とmiRNAに焦点を絞り実施する。①独自に開発したオキシトシン神経系を活性化する内服薬の治療効果と作用を臨床研究により確認する。②miRNAのASDへの関与を解析するため、aCGH解析などにより、疾患関連miRNAを抽出する。③ASDに関連すると確認されたmiRNAについて、脳での発現解析や細胞導入による作用の確認等により作用を解析するとともに、治療二用いる可能性を探る。その一端として、MECP2重複例で、miRNA導入によりMECP2発現量を減らし治療可能となるかを解析する。

Outline of Final Research Achievements

To develop the treatment for neurodevelopmental disorder, double blind test of a functional oligosaccharide that activate oxytocin nervous system to patients with autism spectrum disorder has been performed. So far, adverse events have not observed. After confirming the effects for neuronal function, we will move on to clinical trial.
Four miRNAs were identified to decrease the expression of MECP2 to the level about 60-84% in cultured neuronal cells from model mice hippocampus and also from human iPS cells. After the analysis of off target effects, we select the candidate miRNA to treat MECP2 duplication syndrome. Addition to them, AAV9 vector with MECP2 and SynI promotor that had low promotor activity was injected into cisterna magna of Rett syndrome model mice and improved phenotypes. After confirming these effects, we will plan the clinical trials.

Academic Significance and Societal Importance of the Research Achievements

神経発達症の患者・家族の困難は多く、治療法が待たれている。機能性糖質の臨床研究で治療効果が示されれば、自閉スペクトラム症の治療確立に大きな進歩である。また、この機能性糖質は、オキシトシン神経系を賦活するため、オキシトシンと自閉症状の関連解明に重要な結果である。
神経発達症の症状を示す、MECP2関連疾患のMECP2重複症候群とRett症候群は、MECP2の厳密な発現コントロールが必要である。過剰発現を抑えるmiRNA、発現がないRett症候群患者への低発現プロモーターを用いた発現調節による治療開発は、これらの疾患の治療法ができることに加え、遺伝子治療での遺伝子発現調節に貴重な情報となる。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (27 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (21 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 21 results,  Open Access: 17 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Apomorphine is a potent inhibitor of ferroptosis independent of dopaminergic receptors2024

    • Author(s)
      Miyauchi Akihiko、Watanabe Chika、Yamada Naoya、Jimbo Eriko F.、Kobayashi Mizuki、Ohishi Natsumi、Nagayoshi Atsuko、Aoki Shiho、Kishita Yoshihito、Ohtake Akira、Ohno Nobuhiko、Takahashi Masafumi、Yamagata Takanori、Osaka Hitoshi
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 4820-4820

    • DOI

      10.1038/s41598-024-55293-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unfavorable switching of skewed X chromosome inactivation leads to Menkes disease in a female infant2024

    • Author(s)
      Matsumoto Ayumi、Kano Shintaro、Kobayashi Natsumi、Matsuki Mitsuru、Furukawa Rieko、Yamagishi Hirokazu、Yoshinari Hiroki、Nakata Waka、Wakabayashi Hiroko、Tsuda Hidetoshi、Watanabe Kazuhisa、Takahashi Hironori、Yamagata Takanori、Matsumura Takayoshi、Osaka Hitoshi、Mori Harushi、Iwamoto Sadahiko
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 440-440

    • DOI

      10.1038/s41598-023-50668-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of emotion comprehension in children with autism spectrum disorder and Williams syndrome2023

    • Author(s)
      Ikeda Ayaka、Hakuno Yoko、Asada Kosuke、Ikeda Takahiro、Yamagata Takanori、Hirai Masahiro
    • Journal Title

      Autism Research

      Volume: 16 Issue: 12 Pages: 2378-2390

    • DOI

      10.1002/aur.3053

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of the Social Responsiveness Scale-2 among Individuals with Autism Spectrum Disorder and Williams Syndrome in Japan2022

    • Author(s)
      Hirai Masahiro、Asada Kosuke、Kato Takeo、Ikeda Takahiro、Hakuno Yoko、Ikeda Ayaka、Matsushima Kanae、Awaya Tomonari、Okazaki Shin、Kato Toshihiro、Funabiki Yasuko、Murai Toshiya、Heike Toshio、Hagiwara Masatoshi、Yamagata Takanori、Tomiwa Kiyotaka、Kimura Ryo
    • Journal Title

      Journal of Autism and Developmental Disorders

      Volume: - Issue: 8 Pages: 3176-3184

    • DOI

      10.1007/s10803-022-05740-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The ATRX splicing variant c.21-1G>A is asymptomatic2022

    • Author(s)
      Kojima Karin、Wada Takahito、Shimbo Hiroko、Ikeda Takahiro、Jimbo Eriko F.、Saitsu Hirotomo、Matsumoto Naomichi、Yamagata Takanori
    • Journal Title

      Human Genome Variation

      Volume: 9 Issue: 1 Pages: 33-33

    • DOI

      10.1038/s41439-022-00212-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A TUBB4A Met363Thr variant in pediatric hypomyelination without atrophy of the basal ganglia2022

    • Author(s)
      Hashiguchi Marina、Monden Yukifumi、Nozaki Yasuyuki、Watanabe Kazuki、Nakashima Mitsuko、Saitsu Hirotomo、Yamagata Takanori、Osaka Hitoshi
    • Journal Title

      Human Genome Variation

      Volume: 9 Issue: 1 Pages: 19-19

    • DOI

      10.1038/s41439-022-00198-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent pneumonia in three patients with MECP2 duplication syndrome with aspiration as the possible cause2022

    • Author(s)
      Sugitate Ryo、Muramatsu Kazuhiro、Ogata Tomomi、Goto Masahide、Hayashi Shin、Sawaura Noriko、Kawada-Nagashima Masako、Matsui Atsushi、Yamagata Takanori
    • Journal Title

      Brain and Development

      Volume: 44 Issue: 7 Pages: 486-491

    • DOI

      10.1016/j.braindev.2022.03.005

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Developmental changes of the neural mechanisms underlying level 2 visual perspective‐taking: A functional near‐infrared spectroscopy study2022

    • Author(s)
      Hirai Masahiro、Sakurada Takeshi、Ikeda Takahiro、Monden Yukifumi、Shimoizumi Hideo、Yamagata Takanori
    • Journal Title

      Developmental Psychobiology

      Volume: 64 Issue: 1 Pages: 1-20

    • DOI

      10.1002/dev.22229

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy.2021

    • Author(s)
      Ikeda T, Kawahara Y, Miyauchi A, Niijima H, Furukawa R, Shimozawa N, Morimoto A, Osaka H, Yamagata T.
    • Journal Title

      JIMD Rep.

      Volume: 63 Issue: 1 Pages: 19-24

    • DOI

      10.1002/jmd2.12259

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Valine metabolites analysis in ECHS1 deficiency2021

    • Author(s)
      Kuwajima M, Kojima K, Osaka H, Hamada Y, Jimbo E, Watanabe M, Aoki S, Sato-Shirai I, Ichimoto K, Fushimi T, Murayama K, Ohtake A, Kohda M, Kishita Y, Yatsuka Y, Uchino S, Mimaki M, Miyake N, Matsumoto N, Okazaki Y, Ogata T, Yamagata T, Muramatsu K.
    • Journal Title

      Molecular Genetics and Metabolism Reports

      Volume: 29 Pages: 100809-100809

    • DOI

      10.1016/j.ymgmr.2021.100809

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dopaminergic restoration of prefrontal cortico-putaminal network in gene therapy for aromatic l-amino acid decarboxylase deficiency2021

    • Author(s)
      Onuki Yoshiyuki、Ono Sayaka、Nakajima Takeshi、Kojima Karin、Taga Naoyuki、Ikeda Takahiro、Kuwajima Mari、Kurokawa Yoshie、Kato Mitsuhiro、Kawai Kensuke、Osaka Hitoshi、Sato Toshihiko、Muramatsu Shin-ichi、Yamagata Takanori
    • Journal Title

      Brain Communications

      Volume: - Issue: 3

    • DOI

      10.1093/braincomms/fcab078

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intellectual disability and microcephaly associated with a novel CHAMP1 mutation2021

    • Author(s)
      Asakura Yuta、Osaka Hitoshi、Aoi Hiromi、Mizuguchi Takeshi、Matsumoto Naomichi、Yamagata Takanori
    • Journal Title

      Human Genome Variation

      Volume: 8 Issue: 1 Pages: 34-34

    • DOI

      10.1038/s41439-021-00165-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Greater reliance on proprioceptive information during a reaching task with perspective manipulation among children with autism spectrum disorders2021

    • Author(s)
      Hirai Masahiro、Sakurada Takeshi、Izawa Jun、Ikeda Takahiro、Monden Yukifumi、Shimoizumi Hideo、Yamagata Takanori
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15974-15974

    • DOI

      10.1038/s41598-021-95349-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two cases of DYNC1H1 mutations with intractable epilepsy2021

    • Author(s)
      Matsumoto Ayumi、Kojima Karin、Miya Fuyuki、Miyauchi Akihiko、Watanabe Kazuhisa、Iwamoto Sadahiko、Kawai Kensuke、Kato Mitsuhiro、Takahashi Yukitoshi、Yamagata Takanori
    • Journal Title

      Brain and Development

      Volume: 43 Issue: 8 Pages: 857-862

    • DOI

      10.1016/j.braindev.2021.05.005

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] MCT8 deficiency in a patient with a novel frameshift variant in the SLC16A2 gene2021

    • Author(s)
      Wakabayashi Kei、Osaka Hitoshi、Kojima Karin、Imaizumi Taichi、Yamamoto Toshiyuki、Yamagata Takanori
    • Journal Title

      Human Genome Variation

      Volume: 8 Issue: 1 Pages: 10-10

    • DOI

      10.1038/s41439-021-00142-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings2021

    • Author(s)
      Ohashi K, Fukuhara S, Miyachi T, Asai T, Imaeda M, Goto M, Kurokawa Y, Anzai T, Tsurusaki Y, Miyake N, Matsumoto N, Yamagata T, Saitoh S
    • Journal Title

      J Autism Dev Disord

      Volume: なし Issue: 12 Pages: 4655-4662

    • DOI

      10.1007/s10803-021-04910-3

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene Therapy in a Mouse Model of Niemann?Pick Disease Type C12021

    • Author(s)
      Kurokawa Yoshie、Osaka Hitoshi、Kouga Takeshi、Jimbo Eriko、Muramatsu Kazuhiro、Nakamura Sachie、Takayanagi Yuki、Onaka Tatsushi、Muramatsu Shin-ichi、Yamagata Takanori
    • Journal Title

      Human Gene Therapy

      Volume: 32 Issue: 11-12 Pages: 589-598

    • DOI

      10.1089/hum.2020.175

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intra-cisterna magna delivery of an AAV vector with the GLUT1 promoter in a pig recapitulates the physiological expression of SLC2A12021

    • Author(s)
      Nakamura Sachie、Osaka Hitoshi、Muramatsu Shin-ichi、Takino Naomi、Ito Mika、Jimbo Eriko F.、Watanabe Chika、Hishikawa Shuji、Nakajima Takeshi、Yamagata Takanori
    • Journal Title

      Gene Therapy

      Volume: 28 Issue: 6 Pages: 329-338

    • DOI

      10.1038/s41434-020-00203-z

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Does Culture Shape Face Perception in Autism? Cross-cultural Evidence of the Own-Race Advantage From the UK and Japan2020

    • Author(s)
      Hanley, M., Riby, DM., Derges, MJ, Douligeri, A., Philyaw, Z., Ikeda, T., Monden, Y., Shimoizumi, H., Yamagata, T., Hirai, M.
    • Journal Title

      Developmental Science

      Volume: 25 Issue: 5 Pages: 1-20

    • DOI

      10.1111/desc.12942

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy2019

    • Author(s)
      Negishi Yutaka、Ieda Daisuke、Hori Ikumi、Nozaki Yasuyuki、Yamagata Takanori、Komaki Hirofumi、Tohyama Jun、Nagasaki Keisuke、Tada Hiroko、Saitoh Shinji
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 14 Issue: 1 Pages: 277-277

    • DOI

      10.1186/s13023-019-1249-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex.?2019

    • Author(s)
      Noda M, Iwamoto I, Tabata H, Yamagata T, Ito H, Nagata K.
    • Journal Title

      Sci. Rep.

      Volume: 9 Issue: 1 Pages: 5874-5874

    • DOI

      10.1038/s41598-019-42390-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Gene therapy for Niemann-Pick disease type C1 (NPC1) using AAV.GTX-NPC1.2023

    • Author(s)
      Karin Kojima, Yoshie Kurokawa, Chika Watanabe, Takanori Yamagata.
    • Organizer
      第29回日本遺伝子細胞治療学会学術集会 シンポジウムGenetic Diseases
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 小児難治性神経疾患に対する遺伝子治療2021

    • Author(s)
      山形 崇倫
    • Organizer
      第124回日本小児科学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 遺伝子治療開発における臨床試験の実際2021

    • Author(s)
      山形 崇倫
    • Organizer
      第63回日本小児神経学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Gene therapy of genetic neurological disorders2021

    • Author(s)
      Osaka H,Nakamura S,Kurokawa Y,Kojima K, Miyauchi A,Muramatsu K,Jimbo E,Nakajima T,Mizukami H,Muramatsu SI,Yamagata T
    • Organizer
      第27回日本遺伝子細胞治療学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Circadian-relevant gene PERIOD3 is related to autism spectrum disorder and has function neuronal development2019

    • Author(s)
      Miyauchi A, Noda M, Matsumoto A, Goto M, Kojima K, Osaka H, Jimbo E, Nagata K, Yamagata T
    • Organizer
      The American Society of Human Genetics 2019 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] First report of FER1L6 as the gene responsible for hypotonia and intellectual disability2019

    • Author(s)
      Matsumoto A, Nagao Y, Saitsu H, Osaka H, Iwamoto S, Yamagata T
    • Organizer
      日本人類遺伝学会 第64回大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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