NAKAHARA Jin

写真a

Affiliation

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

Position

Professor

Related Websites

External Links
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Profile 【 Display / hide 】

  • - Japanese Society of Neurology: District Representative and Delegate
    - Japanese Society of Internal Medicine: Councilor
    - Japanese Society of Neuroimmunology: Director
    - Japanese Society of Neurological Therapeutics: Councilor
    - Japanese Society for Neuroinfectious Diseases: Councilor
    - Japan Multiple Sclerosis Network: Director
    - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS): Central organizing committee member
    - American Academy of Neurology (AAN) and European Academy of Neurology (EAN): Member

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Message from the Faculty Member 【 Display / hide 】

  • We aim to develop actual therapeutics by every conceivable means – from advancement of translational research to home care medicine – to improve the quality of life of patients suffering from various neurological diseases.

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Other Affiliation 【 Display / hide 】

  • Keio University Hospital Parkinson's Disease Center, Director

  • Center for Parkinson's Disease Research, Keio University, Director

  • Keio University Hospital Stroke Center, Director

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Career 【 Display / hide 】

  • 2003.04
    -
    2004.03

    慶應義塾大学, COEプログラム（生命科学）, 研究員

  • 2004.04
    -
    2007.03

    独立行政法人日本学術振興会, 特別研究員（DC1）

  • 2007.04
    -
    2008.11

    独立行政法人日本学術振興会, 特別研究員（PD）

  • 2008.12
    -
    2013.03

    慶應義塾大学, 医学部総合医科学研究センター, 特任講師

  • 2013.04
    -
    2018.03

    慶應義塾大学, 医学部内科学教室（神経）, 助教

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Academic Background 【 Display / hide 】

  • 2003.03

    Keio University, School of Medicine

    University, Graduated

  • 2007.03

    Keio University, Graduate School, Division of Medicine, 生理系専攻

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework, 2007.03

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Licenses and Qualifications 【 Display / hide 】

  • Medical license, 2003.05

  • Certified occupational physician, 2011.09

  • Board certified member of the Japanese Society of Internal Medicine, 2013.09

  • Board certified neurologist, 2014.07

  • Fellow of the Japanese Society of Internal Medicine (FJSIM), 2019.12

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Research Areas 【 Display / hide 】

  • Life Science / Neurology

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Research Keywords 【 Display / hide 】

  • Oligodendrocyte

  • Multiple sclerosis

  • Neuroimmunology

  • Neurology

  • Neuromyelitis optica spectrum disorder

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Research Themes 【 Display / hide 】

  • 神経治療学の拠点形成, 

    2018
    -
    Present

  • 多発性硬化症の臨床研究, 

    2011
    -
    Present

  • 中枢神経系髄鞘再生療法の開発, 

    1999
    -
    Present

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Books 【 Display / hide 】

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

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

    　View Summary

    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.

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Papers 【 Display / hide 】

  • CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society

    Takizawa T., Ihara K., Watanabe N., Takemura R., Takahashi N., Miyazaki N., Shibata M., Suzuki K., Imai N., Suzuki N., Hirata K., Takeshima T., Nakahara J.

    Journal of Headache and Pain （Journal of Headache and Pain)  25 （ 1 ）  2024.12

    ISSN  11292369

    　View Summary

    Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. Methods: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. Results: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). Conclusions: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

  • Proteomic insights into extracellular vesicles in ALS for therapeutic potential of Ropinirole and biomarker discovery

    Kato C., Ueda K., Morimoto S., Takahashi S., Nakamura S., Ozawa F., Ito D., Daté Y., Okada K., Kobayashi N., Nakahara J., Okano H.

    Inflammation and Regeneration （Inflammation and Regeneration)  44 （ 1 ）  2024.12

    　View Summary

    Background: Extracellular vesicles (EVs) hold the potential for elucidating the pathogenesis of amyotrophic lateral sclerosis (ALS) and serve as biomarkers. Notably, the comparative and longitudinal alterations in the protein profiles of EVs in serum (sEVs) and cerebrospinal fluid (CSF; cEVs) of sporadic ALS (SALS) patients remain uncharted. Ropinirole hydrochloride (ROPI; dopamine D2 receptor [D2R] agonist), a new anti-ALS drug candidate identified through induced pluripotent stem cell (iPSC)-based drug discovery, has been suggested to inhibit ALS disease progression in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial, but its mechanism of action is not well understood. Therefore, we tried to reveal longitudinal changes with disease progression and the effects of ROPI on protein profiles of EVs. Methods: We collected serum and CSF at fixed intervals from ten controls and from 20 SALS patients participating in the ROPALS trial. Comprehensive proteomic analysis of EVs, extracted from these samples, was conducted using liquid chromatography/mass spectrometer (LC/MS). Furthermore, we generated iPSC-derived astrocytes (iPasts) and performed RNA sequencing on astrocytes with or without ROPI treatment. Results: The findings revealed notable disparities yet high congruity in sEVs and cEVs protein profiles concerning disease status, time and ROPI administration. In SALS, both sEVs and cEVs presented elevated levels of inflammation-related proteins but reduced levels associated with unfolded protein response (UPR). These results mirrored the longitudinal changes after disease onset and correlated with the revised ALS Functional Rating Scale (ALSFRS-R) at sampling time, suggesting a link to the onset and progression of SALS. ROPI appeared to counteract these changes, attenuating inflammation-related protein levels and boosting those tied to UPR in SALS, proposing an anti-ALS impact on EV protein profiles. Reverse translational research using iPasts indicated that these changes may partly reflect the DRD2-dependent neuroinflammatory inhibitory effects of ROPI. We have also identified biomarkers that predict diagnosis and disease progression by machine learning-driven biomarker search. Conclusions: Despite the limited sample size, this study pioneers in reporting time-series proteomic alterations in serum and CSF EVs from SALS patients, offering comprehensive insights into SALS pathogenesis, ROPI-induced changes, and potential prognostic and diagnostic biomarkers.

  • Efficacy and tolerability of 100 mg of lasmiditan for migraine: A multi-center, prospective observational real-world study in Japan

    Ishii R., Ishizuchi K., Watanabe N., Fukazawa R., Trivedi M., Nakahara J., Takizawa T.

    Cephalalgia : an international journal of headache （Cephalalgia : an international journal of headache)  44 （ 6 ）  2024.06

    　View Summary

    BACKGROUND: Real-world data on the effectiveness and safety of lasmiditan, a new medication for acute migraine attacks, is necessary. METHODS: We performed a prospective, observational, multi-center, real-world study. A total of 48 patients with migraine (44 females, 44.6 ± 12.9 years old) were included in this study. RESULTS: Twenty-three patients (47.9%) reported they were headache-free two hours after taking lasmiditan and were categorized into the responder group. In total, 44 patients (91.7%) experienced at least one side effect within two hours of taking the medication. Dizziness, somnolence, malaise, nausea, and palpitations were reported by 56.3% (n = 27), 45.8% (n = 22), 37.5% (n = 18), 20.8% (n = 10), and 14.6% (n = 7) of patients respectively. Of 48 patients, 20 (41.7%) indicated that they preferred lasmiditan to their previous acute treatment. There were no predictive factors for efficacy. CONCLUSION: This real-world study demonstrated the efficacy and safety of lasmiditan. More than 90% of patients experienced side effects from lasmiditan. Approximately 40% of patients preferred lasmiditan despite the occurrence of side effects.

  • Phenotypic Insights Into Anti-IgLON5 Disease in IgLON5-Deficient Mice

    Lee S.Y., Shoji H., Shimozawa A., Aoyagi H., Sato Y., Tsumagari K., Terumitsu M., Motegi H., Okada K., Sekiguchi K., Kuromitsu J., Nakahara J., Miyakawa T., Ito D.

    Neurology(R) neuroimmunology & neuroinflammation （Neurology(R) neuroimmunology & neuroinflammation)  11 （ 3 ）  2024.05

    　View Summary

    BACKGROUND AND OBJECTIVES: Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease. We generated IgLON5 knockout (-/-) mice to investigate the functions of IgLON5 and elucidate the pathomechanism of anti-IgLON5 disease. METHODS: IgLON5 knockout (-/-) mice underwent behavioral tests investigating motor function, psychiatric function (notably anxiety and depression), social and exploratory behaviors, spatial learning and memory, and sensory perception. Histologic analysis was conducted to investigate tau aggregation in mice with tauopathy. RESULTS: IgLON5-/- mice had poorer performance in the wire hang and rotarod tests (which are tests for motor function) than wild-type mice. Moreover, IgLON5-/- mice exhibited decreased anxiety-like behavior and/or hyperactivity in behavior tests, including light/dark transition test and open field test. IgLON5-/- mice also exhibited poorer remote memory in the contextual fear conditioning test. However, neither sleeping disabilities assessed by EEG nor tau aggregation was detected in the knockout mice. DISCUSSION: These results suggest that IgLON5 is associated with activity, anxiety, motor ability, and contextual fear memory. Comparing the various phenotypes of anti-IgLON5 disease, anti-IgLON5 disease might partially be associated with loss of function of IgLON5; however, other phenotypes, such as sleep disorders and tau aggregation, can be caused by gain of function of IgLON5 and/or neuronal damage due to inflammation. Further studies are needed to elucidate the role of IgLON5 in the pathogenesis of anti-IgLON5 diseases.

  • Real-world management of patients with neuromyelitis optica spectrum disorder using satralizumab: Results from a Japanese claims database

    Nakashima I., Nakahara J., Yasunaga H., Yamashita M., Nishijima N., Satomura A., Nio M., Fujihara K.

    Multiple Sclerosis and Related Disorders （Multiple Sclerosis and Related Disorders)  84 2024.04

    ISSN  22110348

    　View Summary

    Background: Satralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. Methods: We used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. Results: Of the 131 patients included in the overall population, most were female (90.8 %), aged 18–65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0–351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. Conclusion: These real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

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

  • Precision medicine research for neuromyelitis optica-spectrum disorders

    2023.04
    -
    2028.03

    基盤研究(B), Principal investigator

  • 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

    2018.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 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

    2013.04
    -
    2016.03

    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

  • 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

    2013.04
    -
    2016.03

    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

  • アストロサイトによるin vivoケトン体生合成機構の解明

    2010.04
    -
    2013.03

    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

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Intellectual Property Rights, etc. 【 Display / hide 】

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

    Date applied： 8252540  2012.08 

    Date issued： 8252540  2012.08

    Patent, Joint

  • Medicinal compositions containing Fc receptor γ chain activator

    Date applied： 7901678  2011.03 

    Date issued： 7901678  2011.03

    Patent, Joint

  • Fc受容体γ鎖活性化物質を含有する医薬組成物

    Date applied： 4214249  2008.11 

    Date issued： 4214249  2008.11

    Patent, Joint

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Awards 【 Display / hide 】

  • Best Presentation Award

    2017, Sendai Conference

  • MSJ-PACTRIMS investigator award

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

  • 優秀指導教官賞

    2014, 日本内科学会

  • MSJ-PACTRIMS Investigator Award

    2014, PACTRIMS

  • 優秀指導教官賞

    2014, 内科学サミット2014

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2024

  • INTERNAL MEDICINE: SEMINAR

    2024

  • INTERNAL MEDICINE: PRACTICE

    2024

  • INTERNAL MEDICINE

    2024

  • CLINICAL CLERKSHIP IN NEUROLOGY

    2024

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Memberships in Academic Societies 【 Display / hide 】

  • 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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