KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

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

Message from the Faculty Member 【 Display / hide 】

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.

Other Affiliation 【 Display / hide 】

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)

• Vice Director, Keio University Hospital Stroke Center

Career 【 Display / hide 】

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 】

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

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

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

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• Medical License, Japan, 2003.05

• Certified Occupational Physician, The Japan Medical Association, 2011.09

• Board Certified Member, The Japanese Society of Internal Medicine, 2013.09

• Board Certified Neurologist, The Japanese Society of Neurology, 2014.07

• JSIM Appointed Physician for Fellowship Training, The Japanese Society of Internal Medicine, 2017.09

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Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Neurology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Oligodendrocyte

• Multiple sclerosis

• Neuroimmunology

• Neurology

• Neuromyelitis optica spectrum disorder

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Research Themes 【 Display / hide 】

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

Books 【 Display / hide 】

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.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• A multicenter, retrospective study in patients with multiple sclerosis treated with natalizumab in a real-world setting in Japan: The REFIND study

  Nakashima I., Ohashi T., Yokoyama K., Kaida K., Nakahara J., Kondo T., Yoshikura N., Shimizu Y., Nohara C., Sakurai K., Yokote H., Niino M., Yamamura T., Fujihara K., Isobe N., Ochi H., Mori M., Kawachi I., Shimizu F., Kanda M., Tani Y., Fukazawa T.

  Multiple Sclerosis and Related Disorders 107 2026.03

  ISSN  22110348

  　View Summary

  Background: Natalizumab (TYSABRI^Ⓡ) is known to be an efficacious treatment at a standard-interval dosing (SID; 300 mg administered intravenously every 4 weeks) for patients with relapsing-remitting sclerosis (RRMS). However, the SID of natalizumab is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Lengthening the time between doses of natalizumab beyond 4 weeks, also known as extended-interval dosing (EID), is associated with lower risk of PML in patients with RRMS, and patients have been switched from SID to EID without meaningful loss of efficacy. In this multicenter, retrospective, observational study, REFIND, we examined real-world natalizumab dosing patterns and MS disease activity in patients with RRMS in Japan. Methods: REFIND retrospectively collected data from medical records of patients at 20 study centers in Japan. Patients with MS aged 20 years and older who received at least one dose of natalizumab after January 1, 2018, and had at least one clinical assessment were included. The primary endpoints were dosing patterns used in clinical practice and MS disease activity by dosing patterns. SID was defined as a mean natalizumab dosing interval ≤35 days, and EID was defined as a mean natalizumab dosing interval ≥36 to ≤84 days. Dosing pattern groups included SID-only, EID-only, or SID followed by EID (SID/EID). For each dosing pattern group, the annualized relapse rate (ARR) before and after administration of natalizumab was compared using a negative binomial regression model. Results: Of the 203 patients with MS eligible for inclusion in the REFIND study, 120 patients with RRMS were treated with natalizumab for ≥1 year, with a mean ± standard deviation (SD) age of 36.0 ± 9.4 years and a mean ± SD administration period of 32.8 ± 18.8 months. Among these patients, 13 had an SID-only natalizumab dosing pattern, 49 had EID-only, and 58 had SID/EID, with mean ± SD dosing intervals of 30.8 ± 1.6 days, 45.9 ± 3.4 days, and 38.7 ± 3.4 days, respectively. Overall ARR 1 year before vs 1 year after initiation of natalizumab was 1.03 vs 0.12 (P < 0.0001). ARR before vs after natalizumab in the SID-only group was 1.08 vs 0.62 (P = 0.378), in the EID-only group was 0.95 vs 0.02 (97.9% reduction, P = 0.0005), and in the SID/EID group was 1.08 vs 0.09 (91.7% reduction, P < 0.0001). Proportions of patients with new or enlarging T2 lesions in the SID-only, and the EID-only, and SID/EID groups were reduced by 89.1%, 83.5%, and 95.7%, respectively, after natalizumab initiation compared with the year before natalizumab. Conclusions: The significant reduction in ARR observed with EID or SID/EID suggests that there is little difference between these dosing regimens in this retrospective dataset in Japan. The effectiveness of natalizumab in reducing the number of new or enlarging T2 lesions was similar across all dosing groups and consistent with known high efficacy of natalizumab in controlling disease activity. These real-world data on natalizumab EID in Japan may help inform treatment choices for Asian populations.

  • Access to Document (DOI)

• A 12-month observational study on the safety, efficacy on migraine-associated symptoms and satisfaction of CGRP monoclonal antibodies in Japanese patients with migraine

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

  Journal of the Neurological Sciences 481 2026.02

  ISSN  0022510X

  　View Summary

  Introduction: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are effective in clinical trials and real-world settings. However, data other than headache frequency remains limited in East Asia. Thus, we investigated long-term efficacy, tolerability, and patient-reported satisfaction of CGRP mAbs in clinical practice. Methods: This single-center observational study included patients with migraine who were administered one of three CGRP mAbs (erenumab, galcanezumab, and fremanezumab) between August 2021 and February 2023. Baseline demographic and headache characteristics were recorded, and treatment outcomes, adverse events, migraine-associated symptoms, and satisfaction levels were assessed over time. Results: We enrolled 150 patients with episodic (n = 81) or chronic migraine (n = 69), including 40 with migraine aura. At six and twelve months, 36/67 (54%) and 22/42 (52%) patients achieved at least 50% reduction in monthly migraine days. Multivariate logistic regression showed that among differences in demographic and headache characteristics between responders and non-responders, the response rate at 3 months was associated with the 6-month response. Migraine-associated symptoms and aura showed improving trends until 5 months after CGRP mAbs initiation. As for safety, injection site reaction was seen in 35/146 (24%), 14/57 (25%), and 4/37 (11%) at 1, 6, and 12 months, respectively. Regarding satisfaction, 74%, 92%, and 94% answered “very satisfied” or “somewhat satisfied” at 1, 6, and 12 months, respectively. Conclusion: This study highlighted the role of early response in predicting the long-term response to CGRP mAbs. We also emphasized the importance of documenting satisfaction, migraine aura frequency, in addition to migraine frequency, for deeper insights into migraine pathophysiology.

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

• 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^® platform, while all other biomarkers were measured using the Simoa^® 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.

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

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

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

• Imaging analysis of myelin pathologies in multiple sclerosis using q-Space myelin map method

  Nakahara, Jin

  科学研究費補助金研究成果報告書 2022

• Designing Asian platform for neuroimmunology

  Nakahara, Jin

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2020

• International collaborative study on novel MRI modality "Myelin map"

  Nakahara, Jin

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2020

• Platform development for neuro-immunological therapeutics in the Asian region.

  Nakahara, Jin

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2019

• Novel therapeutic strategy against ischemic stroke based on glial cell interaction by ketone bodies

  Nakahara, Jin

  科学研究費補助金研究成果報告書 2017

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Correction to: Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis (BMC Neurology, (2025), 25, 1, (1), 10.1186/s12883-024-04009-z)

  Tokuyasu D., Imai S., Chen S.P., Ihara K., Watanabe N., Izawa Y., Nakahara J., Hori S., Takizawa T.

  BMC Neurology 25 ( 1 )  2025.12

  　View Summary

  Following publication of the original article [1], the authors identified an error in the author name of Shih-Pin Chen. The incorrect author name is: Shin-Pin Chen The correct author name is: Shih-Pin Chen The author group has been updated above and the original article [1] has been corrected.

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• A Cautionary Note on the Indication for Deep Brain Stimulation in Parkinsonism Patients With SLC9A6 Gene Mutations

  Okusa S., Tezuka T., Kosugi K., Yamamoto Y., Takahata K., Higuchi M., Akiyama T., Kobayashi M., Toda M., Ito D., Nakahara J., Seki M.

  Journal of Movement Disorders 18 ( 3 ) 268 - 270 2025.07

  ISSN  2005940X

  • Access to Document (DOI)

• Levodopa Pharmacokinetics in Switching From Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in a Patient With Parkinson’s Disease: A Case Report

  Nukariya T., Tezuka T., Okusa S., Okochi R., Sakai Y., Nihei Y., Nakahara J., Seki M.

  Journal of Movement Disorders 18 ( 2 ) 179 - 181 2025.04

  ISSN  2005940X

  • Access to Document (DOI)

• Multiple Genetic Analysis Unravels Pseudoexon in ATP7B in a Patient with Clinically Diagnosed Wilson Disease

  Tezuka T., Miya F., Okusa S., Funayama M., Hattori N., Kosaki K., Nakahara J., Seki M.

  Movement Disorders Clinical Practice  2025

  • Access to Document (DOI)

• Potential Psychosis Induced by a Sustained High Plasma Levodopa Concentration Due to Continuous Subcutaneous Foslevodopa/ Foscarbidopa Infusion in a Patient With Parkinson’s Disease: A Case Report

  Tezuka T., Nukariya T., Kizuka Y., Okusa S., Okochi R., Sakai Y., Nihei Y., Nakahara J., Seki M.

  Journal of Movement Disorders 17 ( 4 ) 453 - 455 2024.10

  ISSN  2005940X

  • Access to Document (DOI)

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

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 】

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

Awards 【 Display / hide 】

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 】

Courses Taught 【 Display / hide 】

• ADVANCED INTERNAL MEDICINE

  2025

• ADVANCED CLINICAL CLERKSHIP IN INTERNAL MEDICINE

  2025

• CLINICAL CLERKSHIP IN INTERNAL MEDICINE (NEUROLOGY)

  2025

• LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

  2025

• INTERNAL MEDICINE: SEMINAR

  2025

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Memberships in Academic Societies 【 Display / hide 】

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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