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 】

• Long-term efficacy and disease-specific responsiveness to protirelin in patients with spinocerebellar degeneration: A retrospective study

  Okusa S., Tezuka T., Nakahara J., Seki M.

  Parkinsonism and Related Disorders 145 2026.04

  ISSN  13538020

  　View Summary

  Introduction: The thyrotropin-releasing hormone (TRH) analog protirelin has short-term benefits for cerebellar ataxia (CA), but its long-term efficacy and the subtype-specific responsiveness of spinocerebellar degeneration (SCD) patients remain unclear. Methods: We retrospectively reviewed the records of 92 SCD patients (273 courses) treated with protirelin between July 2011 and October 2025, including patients with idiopathic CA (IDCA), multiple system atrophy with predominant CA (MSA-C) or parkinsonism (MSA-P), and genetic subtypes including spinocerebellar ataxia (SCA) type 6, SCA31 and dentatorubral-pallidoluysian atrophy (DRPLA). Responders were defined as showing ≥1-point improvement on the Scale for the Assessment and Rating of Ataxia (SARA). Results: Protirelin was effective in 64.1% of subjects, with significant improvement overall (p < 0.001) and significant SARA gains in MSA-C (p = 0.047), IDCA (p = 0.02), and SCA31 (p = 0.01). Change in SARA score (ΔSARA) correlated negatively with age and positively with total protirelin dose in IDCA, and negatively with age and disease duration and positively with baseline SARA score in SCA31. Several IDCA and DRPLA patients maintained clinical benefit for more than 10 years. All MSA-P discontinued protirelin within 2 years and all MSA-C within 5 years; some SCA6, and SCA31 patients continued for ≥5 years. Adverse effects were infrequent (2/92, 2.2%). Conclusion: Protirelin is efficacious in SCD patients and well-tolerated, particularly in slow-progressing phenotypes (IDCA and SCA31); its benefit in rapidly progressing ataxias (MSA-C) may be confined to early disease stages. Prospective studies with standardized dosing and long-term follow-up are warranted to establish evidence-based protocols for TRH-related therapy for CA.

  • Access to Document (DOI)

• Ketone Body Supplementation Exerts Renoprotective Effects Against Adenine-Induced Kidney Injury via OXCT1-Mediated Ketolysis in Mice

  Omachi S., Sugahara S., Horiguchi J., Yasuda-Yamahara M., Kuwagata S., Yamahara K., Tanaka-Sasaki Y., Ida S., Kusaba T., Humphreys B.D., Kufukihara K., Nakahara J., Chin-Kanasaki M., Kume S.

  FASEB Journal 40 ( 6 )  2026.03

  ISSN  08926638

  　View Summary

  Ketone bodies have traditionally been recognized as glucose-sparing energy sources, with hepatic ketogenesis and peripheral ketolysis serving pivotal functions in maintaining energy homeostasis during fasting. Although they are commonly seen as harmful due to their link with ketoacidosis, recent studies emphasize their roles in organ protection. This has sparked interest in their possible use as a treatment for chronic kidney disease (CKD). In this study, we examined both exogenous and endogenous ketone body supplementation in adenine-induced kidney injury in mice. Supplementation with the ketone body precursor 1,3-butanediol significantly improved adenine-induced renal fibrosis, inflammation, and apoptotic cell death. However, genetically deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the key enzyme for ketogenesis, in the liver, kidney, or entire body, and removing Succinyl-CoA:3-ketoacid-CoA Transferase 1 (OXCT1), the enzyme for ketolysis, in the kidney alone, did not affect the severity of adenine-induced kidney damage. In contrast, the protective effects of 1,3-butanediol were partially diminished in mice with kidney-specific OXCT1 deficiency, indicating that OXCT1-mediated ketolysis is at least partly necessary for the renal protection afforded by exogenous ketone body supplementation. These findings suggest that supplementing with exogenous ketone bodies, rather than relying on endogenous hepatic or renal ketone production, protects the kidneys in adenine-induced kidney injury in mice, implying that local ketolysis within the kidney plays a mechanistic role in this protection. Our results highlight the therapeutic potential of exogenous ketone body administration in CKD and offer insights into how renal ketone metabolism helps protect against kidney injury.

  • Access to Document (DOI)

• 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)

• Long-term effectiveness and safety of satralizumab for neuromyelitis optica spectrum disorder in a real-world clinical setting in Japan: A 2.5-year final analysis of a multicenter medical chart review (The SAkuraBeyond Study)

  Fujihara K., Isobe N., Miyamoto K., Niino M., Nakahara J., Hattori S., Tanaka M., Tahara M., Suzumura A., Sakurai K., Yoshikura N., Shiomi K., Ochi H., Nagata E., Deguchi K., Tomizawa Y., Yamashita K., Nagatsuka T., Adachi H., Nakashima I.

  Multiple Sclerosis Journal 32 ( 3 ) 302 - 314 2026.03

  ISSN  13524585

  　View Summary

  Purpose: To evaluate the real-world effectiveness and safety of satralizumab over 2.5 years using medical data charts of satralizumab-treated Japanese patients with aquaporin-4 immunoglobulin-G seropositive neuromyelitis optica spectrum disorder (AQP4[+] NMOSD). Major findings: Overall, 124 patients were evaluated (mean ± standard deviation: age, 51.1 ± 14.0 years; disease duration, 7.0 [6.0] years). At baseline, 72.6%, 16.9%, and 35.5% of patients received oral glucocorticoids (GCs), azathioprine (AZA), and tacrolimus (TAC), respectively. The annualized relapse rate (ARR [95% confidence interval]) decreased from 0.45 (0.34–0.58) within 52 weeks before satralizumab initiation to 0.03 (0.02–0.07) after 130 weeks of satralizumab initiation; relapse-free rate was 91.8% at 130 weeks. Nine patients had nine relapses; seven were re-administered satralizumab after relapse. At 130 weeks, 48.8% of relapse-free patients were not receiving oral GCs (89.3% received ⩽5 mg/day); mean oral GC dose reduced from 10.3 to 2.5 mg/day. In patients receiving AZA and TAC at baseline, 80.0% and 47.1% were no longer receiving AZA and TAC at 130 weeks, respectively. Serious drug reactions occurred in 9.7% of patients (serious infections, 6.5%). Conclusion: The real-world relapse-free rate at 2.5 years was 91.8% (ARR = 0.03) in satralizumab-treated patients with AQP4[+] NMOSD, supporting the relapse-preventive effect of satralizumab without new safety concerns. Registration number: UMIN000050027

  • 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)

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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 】

• Reply: Pathophysiological, methodological, and statistical considerations in CGRP monoclonal antibody therapy: A comment on Imai et al

  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 483 2026.04

  ISSN  0022510X

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

• 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)

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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

• 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

• 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 】

• 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 】

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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