中原 仁 (ナカハラ ジン)




医学部 内科学教室(神経) Department of Neurology, Keio University School of Medicine (信濃町)





プロフィール 【 表示 / 非表示

  • ・日本神経学会 関東甲信越支部代表、代議員ほか
    ・日本内科学会 評議員ほか
    ・日本神経免疫学会 理事ほか
    ・日本神経治療学会 評議員
    ・日本神経感染症学会 評議員
    ・日本多発性硬化症ネットワーク 理事

教員からのメッセージ 【 表示 / 非表示

  • 神経内科領域のあらゆる疾患を対象に、先進的なトランスレーショナル・リサーチから在宅医療まで、手段を問わず患者の生命の質(quality of life)を改善させる治療の具現化に向けた研究を行っている。

その他の所属・職名 【 表示 / 非表示

  • 慶應義塾大学病院パーキンソン病センター, センター長

  • 慶應義塾大学パーキンソン病研究センター, センター長

  • 慶應義塾大学病院脳卒中センター, センター長

経歴 【 表示 / 非表示

  • 2003年04月

    慶應義塾大学, COEプログラム(生命科学), 研究員

  • 2004年04月

    独立行政法人日本学術振興会, 特別研究員(DC1)

  • 2007年04月

    独立行政法人日本学術振興会, 特別研究員(PD)

  • 2008年12月

    慶應義塾大学, 医学部総合医科学研究センター, 特任講師

  • 2013年04月

    慶應義塾大学, 医学部内科学教室(神経), 助教

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学歴 【 表示 / 非表示

  • 2003年03月

    慶應義塾大学, 医学部

    大学, 卒業

  • 2007年03月

    慶應義塾大学, 医学研究科, 生理系専攻

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾大学, 課程, 2007年03月

免許・資格 【 表示 / 非表示

  • 医師免許証, 2003年05月

  • 日本医師会認定産業医, 2011年09月

  • 日本内科学会認定内科医, 2013年09月

  • 日本神経学会認定神経内科専門医, 2014年07月

  • 日本内科学会認定総合内科専門医, 2019年12月


研究分野 【 表示 / 非表示

  • ライフサイエンス / 神経内科学

研究キーワード 【 表示 / 非表示

  • オリゴデンドロサイト

  • 多発性硬化症

  • 神経免疫学

  • 神経内科学

  • 視神経脊髄炎関連疾患

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研究テーマ 【 表示 / 非表示

  • 神経治療学の拠点形成, 


  • 多発性硬化症の臨床研究, 


  • 中枢神経系髄鞘再生療法の開発, 



著書 【 表示 / 非表示

  • Visualization of Myelin for the Diagnosis and Treatment Monitoring of Multiple Sclerosis

    Nakahara J., Advances in Experimental Medicine and Biology, 2019年


    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) affecting more than two million people worldwide. As the exact etiology of MS remains elusive, the diagnosis of MS is made by referring to the McDonald diagnostic criteria, which utilizes MRI as a tool to identify “demyelinated” MS lesions. In particular, hyperintense lesions on T2-weighted images (T2WI) or so-called “T2-lesions” are considered to represent demyelinated MS lesions. T2WI, however, lacks myelin specificity, and moreover, remyelination could not be depicted by the use of such modality. For the accurate diagnosis and treatment decision-making, or for the future development of remyelination therapeutics, imaging tools to visualize myelin-specific signals are mandatory. In this chapter, the current use and the limitation of imaging modalities in MS diagnosis and treatment will be reviewed, with the introduction of new imaging method, namely q-space Myelin Map (qMM), to be used for visualization of demyelination and remyelination in MS.

論文 【 表示 / 非表示

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

    Ihara K., Ohtani S., Watanabe N., Takahashi N., Miyazaki N., Ishizuchi K., Hori S., Takemura R., Nakahara J., Takizawa T.

    Journal of Headache and Pain (Journal of Headache and Pain)  24 ( 1 )  2023年12月

    ISSN  11292369


    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.

  • Acceleration of the Development of Microcirculation Embolism in the Brain due to Capillary Narrowing

    Murata J., Unekawa M., Kudo Y., Kotani M., Kanno I., Izawa Y., Tomita Y., Tanaka K.F., Nakahara J., Masamoto K.

    Stroke (Stroke)  54 ( 8 ) 2135 - 2144 2023年08月

    ISSN  00392499


    BACKGROUND: Cerebral microvascular obstruction is critically involved in recurrent stroke and decreased cerebral blood flow with age. The obstruction must occur in the capillary with a greater resistance to perfusion pressure through the microvascular networks. However, little is known about the relationship between capillary size and embolism formation. This study aimed to determine whether the capillary lumen space contributes to the development of microcirculation embolism. METHODS: To spatiotemporally manipulate capillary diameters in vivo, transgenic mice expressing the light-gated cation channel protein ChR2 (channelrhodopsin-2) in mural cells were used. The spatiotemporal changes in the regional cerebral blood flow in response to the photoactivation of ChR2 mural cells were first characterized using laser speckle flowgraphy. Capillary responses to optimized photostimulation were then examined in vivo using 2-photon microscopy. Finally, microcirculation embolism due to intravenously injected fluorescent microbeads was compared under conditions with or without photoactivation of ChR2 mural cells. RESULTS: Following transcranial photostimulation, the stimulation intensity-dependent decrease in cerebral blood flow centered at the irradiation was observed (14%-49% decreases relative to the baseline). The cerebrovascular response to photostimulation showed significant constriction of the cerebral arteries and capillaries but not of the veins. As a result of vasoconstriction, a temporal stall of red blood cell flow occurred in the capillaries of the venous sides. The 2-photon excitation of a single ChR2 pericyte demonstrated the partial shrinkage of capillaries (7% relative to the baseline) around the stimulated cell. With the intravenous injection of microbeads, the occurrence of microcirculation embolism was significantly enhanced (11% increases compared to the control) with photostimulation. CONCLUSIONS: Capillary narrowing increases the risk of developing microcirculation embolism in the venous sides of the cerebral capillaries.

  • “Missing-piece” sign with dural arteriovenous fistula at craniocervical junction: A case report

    Tezuka T., Nukariya T., Katsumata M., Miyauchi T., Tokuyasu D., Azami S., Izawa Y., Nagoshi N., Fujiwara H., Mizutani K., Akiyama T., Toda M., Nakahara J., Nishimoto Y.

    Journal of Stroke and Cerebrovascular Diseases (Journal of Stroke and Cerebrovascular Diseases)  32 ( 7 )  2023年07月

    ISSN  10523057


    Objectives: Spinal dural arteriovenous fistula (sDAVF) is a rare and often underdiagnosed spinal disease. Early diagnosis is required because the deficits are reversible and delays in treatment cause permanent morbidity. Although the abnormal vascular flow void is a critical radiographic feature of sDAVF, they are not always present. A characteristic enhancement pattern of sDAVF has been recently reported as the “missing-piece” sign which can lead to the early and correct diagnosis. Methods: We presented imaging findings, treatment decisions, and the outcome of a rare case of sDAVF, in which the “missing-piece” sign appeared atypical. Results: A 60-year-old woman developed numbness and weakness in her extremities. Spinal MRI revealed longitudinal hyperintensity in the T2-weighted image, extending from the thoracic level to medulla oblongata. At first, myelopathy with inflammation or tumor was suspected because of the lack of flow voids and vascular abnormalities in CT-angiography and MR-DSA. However, we administered intravenous methylprednisolone and her symptom got worse with the appearance of the “missing-piece” sign. Then, we successfully diagnosed sDAVF by angiography. The “missing-piece” sign was considered to derive from inconsistency of the intrinsic venous system of spinal cord, with the abrupt segments without enhancement. The same etiology was considered in our case. Conclusions: Detecting the “missing-piece” sign can lead to the correct diagnosis of sDAVF, even if the sign appeared atypical.

  • Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization

    Shibata M., Kitagawa S., Unekawa M., Takizawa T., Nakahara J.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  24 ( 14 )  2023年07月

    ISSN  16616596


    Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14–18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

  • Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery

    Morimoto S., Takahashi S., Ito D., Daté Y., Okada K., Kato C., Nakamura S., Ozawa F., Chyi C.M., Nishiyama A., Suzuki N., Fujimori K., Kondo T., Takao M., Hirai M., Kabe Y., Suematsu M., Jinzaki M., Aoki M., Fujiki Y., Sato Y., Suzuki N., Nakahara J., Okano H.

    Cell Stem Cell (Cell Stem Cell)  30 ( 6 ) 766 - 780.e9 2023年06月

    ISSN  19345909


    iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

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総説・解説等 【 表示 / 非表示

競争的研究費の研究課題 【 表示 / 非表示

  • 視神経脊髄炎スペクトラム障害のプレシジョンメディシン基盤確立


    中原 仁, 基盤研究(B), 補助金,  研究代表者

  • ミエリンマップ法を用いた多発性硬化症における髄鞘病理の画像解析


    文部科学省・日本学術振興会, 科学研究費助成事業, 中原 仁, 基盤研究(C), 補助金,  研究代表者

  • 髄鞘の可視化技術による多発性硬化症の病型分類に関する研究


    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  研究代表者

  • 髄鞘を標的とした神経変性疾患・脊髄損傷に対する新規治療戦略に関する研究


    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  研究代表者

  • アストロサイトによるin vivoケトン体生合成機構の解明


    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  研究代表者

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知的財産権等 【 表示 / 非表示

  • Drug delivery system toward demyelinating lesion and biochemical marker of demyelinating lesions

    出願日: 8252540  2012年08月 

    発行日: 8252540  2012年08月

    特許権, 共同

  • Medicinal compositions containing Fc receptor γ chain activator

    出願日: 7901678  2011年03月 

    発行日: 7901678  2011年03月

    特許権, 共同

  • Fc受容体γ鎖活性化物質を含有する医薬組成物

    出願日: 4214249  2008年11月 

    発行日: 4214249  2008年11月

    特許権, 共同

受賞 【 表示 / 非表示

  • Best Presentation賞

    2017年, Sendai Conference

  • MSJ-PACTRIMS investigator award

    2014年, Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)

  • 優秀指導教官賞

    2014年, 日本内科学会

  • MSJ-PACTRIMS Investigator賞

    2014年, 環アジア多発性硬化症治療研究会議

  • 優秀指導教官賞

    2014年, 内科学サミット2014

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担当授業科目 【 表示 / 非表示

  • 内科学(神経)講義


  • 内科学講義


  • 内科学演習


  • 内科学実習


  • 内科学


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所属学協会 【 表示 / 非表示

  • 日本内科学会

  • 日本神経学会

  • 日本神経免疫学会

  • 日本神経治療学会

  • 日本脳卒中学会


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