Takizawa, Tsubasa

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Career 【 Display / hide

  • 2010
    -
    2012

    Kawasaki Municipal Hospital

  • 2016

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Instructor

  • 2016
    -
    2018

    Massachusetts General Hospital, Harvard Medical School

  • 2018
    -
    2020

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Instructor

  • 2020
    -
    Present

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Assitant Professor

Academic Background 【 Display / hide

  • 2004
    -
    2010

    Keio University, School of Medicine

  • 2012
    -
    2016

    Keio University, Graduate School of Medicine

 

Research Areas 【 Display / hide

  • Life Science / General internal medicine

  • Life Science / Neurology

Research Keywords 【 Display / hide

  • Migraine

  • Neurology

  • Cluster Headache

  • Headache

 

Papers 【 Display / hide

  • Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS)

    Harada Sei, Iida Miho, Miyagawa Naoko, Hirata Aya, Kuwabara Kazuyo, Matsumoto Minako, Okamura Tomonori, Edagawa Shun, Kawada Yoko, Miyake Atsuko, Toki Ryota, Akiyama Miki, Kawai Atsuki, Sugiyama Daisuke, Sato Yasunori, Takemura Ryo, Fukai Kota, Ishibashi Yoshiki, Kato Suzuka, Kurihara Ayako, Sata Mizuki, Shibuki Takuma, Takeuchi Ayano, Kohsaka Shun, Sawano Mitsuaki, Shoji Satoshi, Izawa Yoshikane, Katsumata Masahiro, Oki Koichi, Takahashi Shinichi, Takizawa Tsubasa, Maruya Hiroshi, Nishiwaki Yuji, Kawasaki Ryo, Hirayama Akiyoshi, Ishikawa Takamasa, Saito Rintaro, Sato Asako, Soga Tomoyoshi, Sugimoto Masahiro, Tomita Masaru, Komaki Shohei, Ohmomo Hideki, Ono Kanako, Otsuka-Yamasaki Yayoi, Shimizu Atsushi, Sutoh Yoichi, Hozawa Atsushi, Kinoshita Kengo, Koshiba Seizo, Kumada Kazuki, Ogishima Soichi, Sakurai-Yageta Mika, Tamiya Gen, Takebayashi Toru

    Journal of Epidemiology (Japan Epidemiological Association)  advpub ( 0 )  2024

    ISSN  09175040

     View Summary

    <p>The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.</p>

  • Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study.

    Keiko Ihara, Seiya Ohtani, Narumi Watanabe, Nobuyuki Takahashi, Naoki Miyazaki, Kei Ishizuchi, Satoko Hori, Ryo Takemura, Jin Nakahara, Tsubasa Takizawa

    The journal of headache and pain (Journal of Headache and Pain)  24 ( 1 ) 23 - 23 2023.12

    ISSN  11292369

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    BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. METHODS: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients' basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. RESULTS: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. CONCLUSIONS: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.

  • Real-world evidence of fremanezumab for treating migraine in Japan: a retrospective study.

    Seiya Ohtani, Narumi Watanabe, Keiko Ihara, Nobuyuki Takahashi, Naoki Miyazaki, Kei Ishizuchi, Ryo Takemura, Satoko Hori, Jin Nakahara, Tsubasa Takizawa

    BMC neurology (BMC Neurology)  23 ( 1 ) 404 - 404 2023.12

     View Summary

    BACKGROUND: There have been very few real-world studies reported in the literature solely focusing on fremanezumab in Asia. This study aimed to evaluate the efficacy and safety of fremanezumab in a real-world setting in Japan. METHOD: This single-centered, observational, retrospective study examined patients with migraines who received four doses of fremanezumab between December 2021 and August 2022 at Keio University Hospital. We assessed the changes in monthly migraine days, responder rates, and migraine-associated symptoms, as well as injection site reactions and adverse events. RESULT: Twenty-nine patients were enrolled, wherein 79.3% were women. Compared with those at baseline, the monthly migraine days decreased by 5.9 days at 4 months. The 50% responder rate was 55.2% at 4 months. A total of 57.9%, 47.8%, and 65.0% of patients showed improvement in the severity of photophobia, phonophobia, and nausea/vomiting, respectively. Moreover, injection site reactions were the most common adverse events (55.2%). CONCLUSION: Fremanezumab is effective and safe for migraine prevention in Japan. Fremanezumab also improved migraine-associated symptoms in half of the patients.

  • Systemic lupus erythematosus mimicking retinal migraine: a case report.

    Toshiki Tezuka, Mamoru Shibata, Hironari Hanaoka, Yoshikane Izawa, Taku Kikuchi, Kunihiko Akino, Yoko Ozawa, Masataka Saito, Yuko Kaneko, Jin Nakahara, Tsubasa Takizawa

    Cephalalgia : an international journal of headache (Cephalalgia)  43 ( 12 ) 3331024231219477 - 3331024231219477 2023.12

    ISSN  03331024

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    BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

  • Switching between anti-calcitonin gene-related peptide monoclonal antibodies: A comparison of monthly and quarterly dosing.

    Keiko Ihara, Seiya Ohtani, Narumi Watanabe, Nobuyuki Takahashi, Naoki Miyazaki, Ryo Takemura, Satoko Hori, Jin Nakahara, Tsubasa Takizawa

    Journal of the neurological sciences (Journal of the Neurological Sciences)  453   120811 - 120811 2023.10

    ISSN  0022510X

     View Summary

    BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have dramatically changed preventive treatment options for patients with migraine. Although there is emerging real-world evidence on the use of CGRPmAbs globally, the change in efficacy and safety after switching between CGRPmAbs owing to patients' frequency of hospital visits preference remains unknown. METHODS: We conducted a single-centre, retrospective, real-world study of patients with migraine who first received galcanezumab for 3 or 4 months and then switched to fremanezumab at Keio University Hospital. We investigated changes in monthly migraine days (MMD), responder rate, and adverse effects such as injection site reactions. RESULTS: MMD increased only by 0.7 (95% CI, -4.1-5.5; p = 0.748) after 4 months of treatment with fremanezumab (6.1, 95% CI, 2.3-9.9) compared to before switching (5.4, 95% CI, 2.2-8.6). Furthermore, switching from galcanezumab to fremanezumab produced only minor adverse events, such as injection site reactions. CONCLUSIONS: After switching from galcanezumab to fremanezumab out of the desire to visit the hospital less often, the reduction in MMD compared to baseline was sustained, and no serious adverse effects were observed.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Investigation of anti-CGRP monoclonal antibodies and novel therapeutics for migraine

    2022.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Principal investigator

  • 中枢神経障害下でのNG2グリアの挙動と髄鞘の再生機序の解明

    2021.04
    -
    2024.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(C), No Setting

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    脳は約 140 億個の神経細胞、その 10 倍のグリア細胞からなり、栄養を供給する脳血管と互いに連絡を取りながら神経グリア血管ユニット(neuro-glio-vascular unit; NVU)を形成している。本実験では分化・再生能が高く、髄鞘を形成するオリゴデンドロサイトや周皮細胞、アストロサイトに分化するオリゴデンドロサイト前駆細胞(OPC)として存在するNG2グリアに焦点を当て、慢性頭窓下の同一部位を長期間反復して観察することによって成体における細胞および髄鞘の形態、脳虚血などの病態時の形態学的変化、髄鞘再生を促進あるいは抗炎症作用を増強するメカニズムを検討し、病態改善のための薬剤の探索とその作用機序の解明を目的とする。
    NG2と高い共発現が確認され、OPCおよびオリゴデンドロサイトに発現するされるSox10に蛍光タンパク質Venusを発現させたマウスにTomita-Seylaz法による慢性頭窓を作成し、二光子顕微鏡を用いて長期間観察を行うことにより、細胞レベルでの変化を経日的に観察した。キレート剤であるクプリゾン混餌食(0.2%)を給餌することにより脱髄モデルを作成し、スルホローダミン101の投与によって生体染色されるアストロサイトの形態学的変化を追跡する手法を確立した。観察終了後に脳を摘出し、蛍光細胞や神経細胞の撮像や解析の手法を検討中である。さらに、実験的脳梗塞モデルである中大脳動脈閉塞術を施行した病態モデルマウスを作成するため、基本的な手技を習得するとともに、線条体や大脳皮質における脳血流の変化と梗塞巣の形成との相関、施行時に発生して梗塞巣の形成に影響を及ぼすと考えられている大脳皮質拡延性脱分極(CSD)との関連についても検討した。

  • 脳血管内皮透過性制御機構の解明による新規神経疾患治療法の確立

    2021.04
    -
    2024.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(C), No Setting

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    脳血管障害は要介護状態となる原因疾患の第一位を占め、2018年に成立した「脳卒中・循環器病対策基本法」の基本理念である、健康寿命延伸の観点から大きな社会的問題となっている。血管内治療など超急性期脳梗塞治療の進歩は目覚ましいが、脳梗塞の発症予防は、いまだ抗血栓療法と血圧管理などに依存し、新規治療法は久しく開発されていない。抗血栓療法は脳出血発症リスクと表裏一体であるなど、脳血管障害の治療で解決すべき課題は多く、脳血管性認知症に至っては治療法が存在しない。安全性と有効性を両立した脳血管障害、さらには脳血管性認知症に対する治療の確立は喫緊の課題である。
    本研究は、内皮に血栓が生じる機序、血管が破綻する機序、神経組織が機能低下する機序の解明を目的とし、脳血管透過性亢進モデルマウスを用いて、血管透過性調節による脳血管障害・血管性認知症の新たな治療概念確立を目指すものである。これにより実臨床で用いられる各抗血栓薬の有効性と安全性の違いや特徴を統一的に説明する理論の確立も目指す。 2021年度は本研究の先行研究結果をまとめた共著論文が提出され、血栓形成(止血)作用を持つトロンビンが脳微小血管障害(血管透過性亢進作用)により脳出血リスクを上昇させる可能性を示したが、これは直感的に想定されるトロンビン作用と真逆の視点を提唱するものである。また、トロンビンが脳微小血管の透過性を上昇させる様子をin vivo、生存下で連続(経時)的に捉えることに成功した。2020年度までの研究成果報告書では統計解析上は、本研究の実験仮説が誤りである可能性も否定できない状況であったが、実験手法改善により、仮説からの予測と一致する結果が蓄積され、統計的評価にも頑健であった。このように、本研究が目標とする「血管透過性制御機構」の解明という観点から、提唱する理論的仮説が真である蓋然性が一定程度高まるデータが得られた。

  • 片頭痛のトリガーの実態調査と解明

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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    片頭痛は若年者に好発する慢性頭痛疾患であり、有病率、生活支障度ともに高い。片頭痛患者の一部ではストレス、生活習慣、天候の変化など何らかの頭痛発作のトリガーを有している。本研究では片頭痛のトリガーの調査を行い、その一部については片頭痛の動物モデルとして広く認知されている皮質拡延性脱分極(Cortical Spreading Depolarization, CSD)(Harriott AM, Takizawa T, Chung DY, Chen SP. Spreading depression as a preclinical model of migraine. J Headache Pain 2019; 20: 45)を用いて科学的な検証を試みる。片頭痛のトリガーについて総合的な解明を行い、最終的には患者QOLの向上を目指す。
    慶應義塾大学病院頭痛外来に通院中の頭痛患者について、約50項目の頭痛のトリガー候補についての調査結果を学会で発表、解析についても進めた。
    さらに慶應義塾大学病院の看護系職員のCOVID-19ワクチン接種後の頭痛の特徴や頻度について調査した。普段から頭痛もちの方においては、COVID-19ワクチン接種後に副反応として頭痛が生じやすいことを明らかにし、国際頭痛学会誌に報告した(Sekiguchi K et al. Incidence of headache after COVID-19 vaccination in patients with history of headache: a cross sectional study. Cephalalgia 2022; 42: 266-272)。
    片頭痛の動物モデル(CSDの測定系)を用いたトリガーに関する研究も進めた。喫煙を負荷した雌マウスにおいてはCSDが惹起されやすいことが明らかとなった。

Awards 【 Display / hide

  • Frontiers in Headache Research Scholarship

    2018, American Headache Society

  • Kitamura Award

    2014, The Japanese Headache Society

 

Courses Taught 【 Display / hide

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2023

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2022

  • 医学概論(ヒトの構造・機能・病態概論)

    2021

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