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

Profile 【 Display / hide 】

  • - Japanese Society of Neurology: 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
    - Japanese Society of Microcirculation: Director
    - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS): Executive committee member
    - American Academy of Neurology (AAN): FAAN
    - European Academy of Neurology (EAN): Corresponding 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 】

  • Guest Professor, Kanazawa University

  • Guest Professor, The JIKEI University School of Medicine

  • Director, iPS Cell Research Center for Intractable Neurological Diseases, Keio University (KiND)

  • Director, Keio University Hospital Parkinson's Disease Center

  • Keio University Hospital Stroke Center

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Career 【 Display / hide 】

  • 2003.04
    -
    2004.03

    COE Researcher, Keio University

  • 2004.04
    -
    2007.03

    JSPS Researcher (DC1), JSPS

  • 2007.04
    -
    2008.11

    JSPS Researcher (PD), JSPS

  • 2008.12
    -
    2013.03

    Project Assistant Professor, Keio University

  • 2013.04
    -
    2018.03

    Instructor, Keio University

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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 】

  • Six-year safety and efficacy outcomes with first-line ofatumumab in recently diagnosed treatment-naive patients with relapsing multiple sclerosis

    Hauser S.L., Freedman M.S., Nakahara J., Paling D., de Seze J., Li J., Abeyewickreme A., Wu M., Sullivan R., Pardo G., Montalban X., Wiendl H.

    Multiple Sclerosis and Related Disorders 105 2026.01

    ISSN  22110348

    　View Summary

    Background: We report ofatumumab's longer-term safety and efficacy in recently diagnosed (≤3 years) treatment-naive (RDTN) people living with relapsing multiple sclerosis (plwRMS). Methods: Safety analyses included RDTN participants receiving at least 1 ofatumumab dose in ASCLEPIOS I/II or other ALITHIOS feeder studies (APLIOS and APOLITOS). Efficacy analyses included participants randomised to ofatumumab in ASCLEPIOS I/II and treated continuously for up to 6 years. Efficacy outcomes include annualised relapse rate (ARR), MRI lesions, no evidence of disease activity-3 (NEDA-3), cognitive processing speed, and work status. Results: The safety analysis included 409 RDTN plwRMS. Exposure-adjusted incidence rates of serious infections and malignancies did not increase to the cut-off date (25-Sep-2025) of 6 years. Over 6 years, mean IgG levels remained stable and IgG was above the lower limit of normal (LLN: 5.65 g/L) in 98.0% of participants at all assessments; mean IgM levels decreased but IgM remained above LLN (0.4 g/L) in 64.1% of participants at all assessments. Of 314 RDTN participants receiving ofatumumab in ASCLEPIOS I/II (efficacy analysis), 233 entered ALITHIOS, and at data cut-off 181 (77.7%, 181/233) were still receiving ofatumumab. ARR decreased from 0.112 (Year 1) to 0.030 (Year 6). An almost complete suppression of MRI lesions was observed up to Year 6. NEDA-3 at Year 6 was observed in 94.4% of participants. At 6 years, up to 70.6% of participants experienced clinically meaningful improvement in cognitive processing speed. Reduced work absenteeism versus baseline was observed. Conclusions: Findings support ofatumumab's highly favourable longer-term benefit-risk profile as first-line therapy for plwRMS.

  • Plasma biomarkers for early detection of alzheimer’s disease: a cross-sectional study in a Japanese cohort

    Kubota M., Bun S., Takahata K., Kurose S., Momota Y., Iwabuchi Y., Tezuka T., Tabuchi H., Seki M., Yamamoto Y., Shikimoto R., Mimura Y., Hoshino T., Shimohama S., Suzuki N., Morimoto A., Oosumi A., Hoshino Y., Tai K., Aoyagi H., Sato Y., Kuromitsu J., Nakahara J., Mimura M., Ito D.

    Alzheimer S Research and Therapy 17 ( 1 )  2025.12

    　View Summary

    Background: Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma biomarkers for diagnosing and staging AD in a Japanese cohort. Methods: The assessed plasma biomarkers included Aβ42/40, phosphorylated tau (p-tau181 and p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), individually and in combination. Aβ42/40 was measured using the HISCL<sup>®</sup> platform, while all other biomarkers were measured using the Simoa<sup>®</sup> platform. Participants were classified based on Aβ PET imaging and neuropsychological testing into healthy controls (HC), AD continuum (preclinical AD, mild cognitive impairment [AD-MCI], and mild dementia [AD-D]), and non-AD cognitive impairment (CI) groups. Receiver operating characteristic analyses were performed to predict the Aβ PET status, correlation with Centiloid (CL) values and cognitive scores, and biomarker comparisons across AD stages. Results: Sixty-nine HC, 13 preclinical AD, 38 AD-MCI, 44 AD-D, and 79 non-AD CI participants were included. The area under the curves (AUCs) for predicting Aβ PET status were 0.937 (Aβ42/40), 0.926 (p-tau217), and 0.946 (p-tau217/Aβ42); results of pair-wise DeLong tests revealed no significant differences among these three metrics (all p > 0.05). In the cognitively normal group, the AUCs were 0.968 (Aβ42/40), 0.958 (p-tau217), and 0.979 (p-tau217/Aβ42), while in the cognitively impaired group, they were 0.919 (Aβ42/40), 0.893 (p-tau217), and 0.923 (p-tau217/Aβ42). Among HC and AD continuum participants, CL correlations were − 0.74 (Aβ42/40), 0.81 (p-tau217), and 0.83 (p-tau217/Aβ42). In the HC and AD continuum, Aβ42/40 levels showed a bimodal distribution (cutoff = 0.096), with a shift from high to low occurring at 19.3 CL, compared to the PET positivity threshold of 32.9 CL. P-tau217 exhibited a linear increase with disease progression. All biomarkers correlated strongly with logical memory scores. Conclusions: Plasma biomarkers, Aβ42/40 and p-tau217, and particularly their ratio (p-tau217/Aβ42), show strong potential as Aβ PET alternatives for AD diagnosis. HISCL-based plasma Aβ42/40 detects Aβ accumulation earlier than Aβ PET visual reading threshold, underscoring its utility as an early diagnostic marker.

  • Effect of lacosamide on cortical spreading depolarization in mice

    Iba C., Unekawa M., Ihara K., Izawa Y., Nakahara J., Takizawa T.

    Journal of Headache and Pain 26 ( 1 )  2025.12

    ISSN  11292369

    　View Summary

    Background: Antiseizure medications are often used as preventive treatment of migraine in appropriate cases; however, the efficacy of lacosamide (LCM), a sodium channel blocker, in preventing migraine attacks remains unclear. Cortical spreading depolarization (CSD) refers to a wave of slowly propagating depolarization across the cerebral cortex. CSD animal models have been extensively used to investigate migraine attacks and evaluate the effects of migraine medication. Herein, we examined the effects of single dose LCM (40 mg/kg) on CSD sensitivity in a mouse model. Findings: Thirty-two C57BL/6 mice (male, n = 16; female, n = 16) were intraperitoneally injected with either LCM (40 mg/kg) or saline before CSD sensitivity testing. Potassium chloride (KCl) was administered to induce CSD, and the CSD threshold, frequency, and propagation velocity were determined. The average CSD frequency induced by 1 M KCl was significantly lower (p = 0.030) and the CSD propagation velocity tended to be lower in the female LCM group than in the saline group. However, no significant differences were observed in any of the three CSD parameters in male mice. Conclusions: In female mice, single dose LCM treatment significantly reduced CSD frequency induced by KCl. Further investigations are warranted to assess the clinical potential of LCM in preventing migraine.

  • Natalizumab-Associated Progressive Multifocal Leukoencephalopathy After Natalizumab Extended Interval Dosing Therapy in Japan

    Takahashi K., Nakahara J., Miura Y., Ae R., Nakamichi K., Harada M., Mori K., Sanjo N., Yukitake M., Yokote H., Hamaguchi T., Yamada M., Takao M.

    Neurology Neuroimmunology and Neuroinflammation 12 ( 6 )  2025.11

    　View Summary

    Objective To describe 5 confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan. Methods The Nationwide PML Surveillance Committee requires mandatory registration of all natalizumab cases and reporting by affiliated facilities conducting JC DNA testing. Suspected PML cases were reviewed by the committee and classified as definite, probable, possible, or non-PML based on established diagnostic criteria. Results From 2016 to 2024, the nationwide PML surveillance committee identified 8 NTZ-PML cases, of which 5 (all women and relapsing-remitting types) were registered as clinically definite PML cases. Four cases involved a switch from other disease-modifying drugs, while one involved natalizumab as the first-line treatment for multiple sclerosis (MS). In all cases, extended interval dosing therapy (EID) every 6–8 weeks was administered for at least 1 year before PML onset, and 3 cases had received EID from the outset. At PML onset, the viral DNA levels in the CSF were ≤100 copies/mL in 3 cases. Discussion Given the high prevalence of JC virus antibody positivity in Japan, additional risk factors may contribute to NTZ-PML susceptibility. Although EID of natalizumab is expected to reduce PML risk, its effectiveness may be limited, particularly in Japanese individuals with high JC virus antibody titers. Introduction Natalizumab is highly effective in preventing relapses in multiple sclerosis (MS)<sup>1</sup>; however, natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) is a concern.<sup>2</sup> Recently, an extended interval dosing (EID) regimen, involving natalizumab administration every 6–8 weeks, has been introduced to reduce the risk of NTZ-PML without compromising therapeutic efficacy.<sup>2,3</sup>

  • Electroconvulsive Therapy Can Prevent a Worsening of Psychosis and Dystonic Voice in PRKN-associated Parkinson’s Disease

    Tezuka T., Daida K., Nakajima S., Konishi M., Nihei Y., Funayama M., Billingsley K.J., Blauwendraat C., Hattori N., Uchida H., Nakahara J., Seki M.

    Internal Medicine 64 ( 21 ) 3155 - 3157 2025.11

    ISSN  09182918

    　View Summary

    Electroconvulsive therapy (ECT), an established treatment for psychiatric disorders, shows promise in alleviating both motor and non-motor symptoms in patients with Parkinson’s disease (PD). We herein report a case of PRKN-associated PD presenting with characteristic psychosis and dystonic voice, which was effectively managed with maintenance ECT. A genetic analysis initially identified a single heterozygous PRKN deletion using multiple ligation-probe amplification. Subsequent Oxford Nanopore technology long-read sequencing revealed a second pathogenic variant, confirming a compound heterozygous PRKN mutation. This case highlights the utility of long-read sequencing in resolving genetic diagnoses and the potential of maintenance ECT for managing complex PD phenotypes.

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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)

    2025

  • INTERNAL MEDICINE: SEMINAR

    2025

  • INTERNAL MEDICINE: PRACTICE

    2025

  • INTERNAL MEDICINE

    2025

  • CLINICAL CLERKSHIP IN NEUROLOGY

    2025

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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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