Details of the Researcher

PHOTO

Ayumi Nishiyama
Section
Tohoku University Hospital
Job title
Assistant Professor
Degree

Research Interests 25

  • エクソーム解析

  • iPS細胞

  • 運動ニューロン疾患

  • FTD

  • 遺伝型

  • 表現型

  • X染色体不活化

  • ゲノム

  • 遺伝性ジストニア

  • KIF5A

  • TBK1

  • 全ゲノム解析

  • ターゲットリシークエンス

  • 網羅的遺伝子解析

  • リピート伸長

  • ALS原因遺伝子

  • ALS

  • OPTN

  • TARDBP

  • FUS

  • 神経変性

  • 運動ニューロン

  • SOD1

  • 次世代シークエンサー

  • 家族性ALS

Research Areas 3

  • Life sciences / Genetics /

  • Life sciences / Medical biochemistry /

  • Life sciences / Neurology /

Papers 43

  1. Three case reports of optic perineuritis complicated by ocular scleritis and hypertrophic pachymeningitis. International-journal

    Momoka Yoshida, Kimihiko Kaneko, Genta Kumada, Chihiro Sasaki, Maki Suzuki, Takuro Shiga, Naohiro Sakamoto, Shio Mitsuzawa, Yuki Matsumoto, Hirohiko Ono, Ayumi Nishiyama, Naoto Sugeno, Noriko Himori, Tatsuro Misu, Toru Nakazawa, Masashi Aoki

    Journal of neuroimmunology　418　578974-578974　2026/05/17

    DOI： 10.1016/j.jneuroim.2026.578974 　

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    Optic perineuritis (OPN) is an uncommon form of the orbital inflammatory disease targeting the optic nerve sheath, which is distinct from optic neuritis. It causes reduced visual acuity and ocular pain and is linked to infection or autoimmunity, including myelin oligodendrocyte glycoprotein-associated disease, but 30-50% are idiopathic. We report three cases of OPN with ocular scleritis and hypertrophic pachymeningitis occurring together or sequentially; in one, pachymeningitis extended from the optic sheath, in two, it was separate. Case 1: 54-year-old man with a history of ocular scleritis developed left ocular pain, diplopia, and visual loss. MRI showed left optic sheath hyperintensity and dural enhancement. Serology and CSF were unremarkable. Intravenous methylprednisolone (IVMP) followed by prednisolone (PSL) improved visual accuracy to 20/13, with no relapse at 10 months on tapering PSL. Case 2: 76-year-old man developed ocular scleritis, OPN, and hypertrophic pachymeningitis presenting as orbital apex syndrome. Blood examination showed pancytopenia. After the treatment of concomitant pneumonia, IVMP partially improved symptoms. Later, he was also diagnosed as myelodysplastic syndrome. He did not relapse without further immunotherapy. Case 3: 63-year-old woman with previous history of ocular scleritis developed acute right visual loss. MRI showed optic sheath and connected dural enhancement. IVMP followed by PSL treatment improved vision from no light perception to 20/125, without relapse at 7 months. These cases suggested possible shared connective-tissue autoimmunity, and warrant attention to the overlap of the three diseases.

  2. Gadolinium enhancement of the cauda equina in a case of familial ALS with p.S135G SOD1 mutation

    Sumika Nomizo, Junji Komatsu, Ayano Shima, Daiki Muramatsu, Keitaro Matsubara, Ichiro Nozaki, Moeko Noguchi-Shinohara, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Kenjiro Ono

    Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration　2026/03/05

    DOI： 10.1080/21678421.2026.2638591 　

  3. Jacifusen for FUS-ALS: molecular effects and clinical outcomes in a case series. International-journal

    Naoki Suzuki, Ayumi Nishiyama, Satoru Ebihara, Masashi Aoki

    Lancet (London, England)　405　(10494)　2028-2030　2025/06/07

    DOI： 10.1016/S0140-6736(25)01038-4 　

  4. MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism. International-journal

    Alan Mejia Maza, Madison Hincher, Kevin Correia, Tammy Gillis, Ayumi Nishiyama, Ellen B Penney, Aloysius Domingo, Rachita Yadav, Micaela G Murcar, Patrick D Villafria Mercado, Justin S Han, Ean P Norenberg, Cara Fernandez-Cerado, G Paul Legarda, Michelle Sy, Edwin Muñoz, Mark C Ang, Cid Czarina E Diesta, Criscely Go, Nutan Sharma, D Cristopher Bragg, Michael E Talkowski, Marcy E MacDonald, Jong-Min Lee, Laurie J Ozelius, Vanessa Chantal Wheeler

    bioRxiv : the preprint server for biology　2025/05/16

    DOI： 10.1101/2025.05.14.653432 　

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    X-linked dystonia parkinsonism (XDP) is a progressive adult-onset neurogenerative disorder caused by the insertion of a SINE-VNTR-Alu (SVA) retrotransposon in TAF1 gene. One element of the SVA is a tandem polymorphic CCCTCT repeat tract whose length inversely correlates with the age of disease onset. Previous observations that the repeat exhibits length-dependent somatic expansion and that XDP onset is modified by variation in DNA repair gene MSH3 indicated that somatic repeat expansion is an important disease driver. Here, we sought to uncover genetic modifiers of CCCTCT instability in XDP patients and to provide a mechanistic link between somatic instability and disease. We determined quantitative metrics of both repeat expansion and repeat contraction in blood. Using genetic association analyses of exome sequencing data, as well as directed sequencing of a variant MSH3 repeat, we found that MSH3 modifies repeat expansion and contraction in blood as well as age at onset. MSH3 alleles associated with earlier disease onset were associated with more expansion and less contraction. Conversely, alleles associated with later disease onset were associated with less expansion and more contraction. Notably, MSH3 repeat alleles were also similarly associated with expansion and contraction in brain tissues. Our findings provide key evidence that MSH3's role(s) in CCCTCT repeat dynamics underlies its impact on clinical disease and indicate that therapeutic strategies to lower or inhibit MSH3 are predicted to both slow CCCTCT expansion and promote CCCTCT contraction, impacting the disease course prior to clinical onset.

  5. The Vodka Trial: Clinical and Genetic Characteristics of Alcohol Responsiveness in Laryngeal Dystonia. International-journal

    Lena C O'Flynn, Aloysius Domingo, Azadeh Hamzehei Sichani, Ayumi Nishiyama, Madison Hincher, Rachita Yadav, Laurie J Ozelius, Kristina Simonyan

    Movement disorders clinical practice　2025/04/23

    DOI： 10.1002/mdc3.70097 　

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    BACKGROUND: Laryngeal dystonia (LD) is isolated task-specific focal dystonia, predominantly impairing speech production. Clinical observations and population survey studies have reported that up to 58% of patients with LD may have symptom improvement following alcohol intake. OBJECTIVES: To determine the objective characteristics of alcohol responsiveness in LD using a standardized alcohol challenge test and genetic testing. METHODS: A total of 109 patients with isolated focal LD participated in the study. Patients were administered two non-diluted drinks of 40-proof vodka 30 min apart, followed by assessments of voice symptoms, breath alcohol content, and side effects. Patients were considered alcohol-responsive (EtOH+) if their symptoms changed by ≥10% from baseline. Whole-exome sequencing was performed to identify genetic variants associated with the alcohol responsiveness of LD. RESULTS: All patients tolerated the standardized alcohol challenge test without major adverse events. Fifty-two patients (47.7%) had an average of 44.4 ± 25.0% improvement of LD symptoms about 45 min after alcohol intake. Five genetic variants in GABAergic pathway-related genes were enriched in EtOH+ patients, and two of these, rs11644926 (ADCY7) and rs2230741 (ADCY9), were associated with the improvement of dystonic voice symptoms. CONCLUSIONS: Alcohol responsiveness of LD symptoms is a robust feature related to the genes regulating the GABAergic synapses. This finding provides support for the evaluation of novel oral medications with mechanisms of action similar to alcohol for the treatment of patients with alcohol-responsive dystonia.

  6. Swift induction of human spinal lower motor neurons and robust ALS cell screening via single-cell imaging. International-journal

    Selena Setsu, Satoru Morimoto, Shiho Nakamura, Fumiko Ozawa, Kagistia Hana Utami, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Yukio Takeshita, Yukihide Tomari, Hideyuki Okano

    Stem cell reports　20　(1)　102377-102377　2025/01/14

    DOI： 10.1016/j.stemcr.2024.11.007 　

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    This study introduces a novel method for rapidly and efficiently inducing human spinal lower motor neurons (LMNs) from induced pluripotent stem cells (iPSCs) to eventually elucidate the pathomechanisms of amyotrophic lateral sclerosis (ALS) and facilitate drug screening. Previous methods were limited by low induction efficiency, poor LMN purity, or labor-intensive induction and evaluation processes. Our protocol overcomes these challenges, achieving around 80% induction efficiency within just two weeks by combining a small molecule-based approach with transcription factor transduction. Moreover, to exclude non-LMN cells from the analysis, we utilized time-lapse microscopy and machine learning to analyze the morphology and viability of iPSC-derived LMNs on a single-cell basis, establishing an effective pathophysiological evaluation system. This rapid, efficient, and streamlined protocol, along with our single-cell-based evaluation method, enables large-scale analysis and drug screening using iPSC-derived motor neurons.

  7. Updated Genetic Analysis of Japanese Familial ALS Patients Carrying SOD1 Variants Revealed Phenotypic Differences for Common Variants. International-journal

    Ayumi Nishiyama, Tetsuya Niihori, Naoki Suzuki, Rumiko Izumi, Tetsuya Akiyama, Masaaki Kato, Ryo Funayama, Keiko Nakayama, Hitoshi Warita, Yoko Aoki, Masashi Aoki

    Neurology. Genetics　10　(6)　e200196　2024/12

    DOI： 10.1212/NXG.0000000000200196 　

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    BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease. Approximately 10% of ALS cases are familial, and more than 20 causative genes have been identified. As we have previously reported, SOD1 variants are the most common causes of familial ALS in Japan. Because antisense oligonucleotides for SOD1-linked ALS are being used in practical applications, the types of variants and the clinical features of patients need to be updated. METHODS: We consecutively recruited 160 families with familial ALS in Japan. We performed genetic analyses, focusing on SOD1-linked ALS as the most common in our cohort, updated their genotypes, and characterized clinical phenotypes. RESULTS: A total of 26 SOD1 variants in 56 patients and 49 families (30.6%) were collected, with the 3 most common (p.His47Arg [the conventional numbering; H46R], p.Leu127Ser [L126S], p.Asn87Ser [N86S]) accounting for 38.8% of all families. We also identified 2 novel variants (p.Ile36Phe [I35F] and p.Asn132Argfs*3 [N131Rfs*3]). The mean age at onset was 48.9 ± 12.2 (mean ± SD) years for all patients with SOD1-linked ALS. Lower limb onset comprised 70% of cases. The mean disease duration was 64.7 ± 82 months, and the median survival was 71.5 months. Some variants led to a relatively homogeneous phenotype, although clinical characteristics differed among types of variants and families. Patients with p.His47Arg (H46R) showed slower progression with lower limb onset and a predominance of lower motor neuron involvement. The p.Leu127Ser (L126S) variant led to varying degrees of progression in heterozygous or homozygous states and presented incomplete penetrance. Intrafamilial phenotypic differences were observed in families carrying p.Asn87Ser (N86S). Four variants (p.Cys7Gly [C6G], p.His44Arg [H43R], p.Leu85Val [L84V], and p.Cys147Arg [C146R]) were found to be associated with rapid disease progression. DISCUSSION: The genetic basis of familial ALS, at least for SOD1 variants, still differed by geographic and ethnic background. Understanding these clinical profiles will help optimize evaluation in targeted gene therapy worldwide and benefit efficient diagnosis, leading to precise application in clinical practice.

  8. Genetic risk variants in New Yorkers of Puerto Rican and Dominican Republic heritage with Parkinson's disease. International-journal

    Gabriel Miltenberger-Miltenyi, Roberto A Ortega, Aloysius Domingo, Rachita Yadav, Ayumi Nishiyama, Deborah Raymond, Viktoriya Katsnelson, Nikita Urval, Matthew Swan, Vicki Shanker, Joan Miravite, Ruth H Walker, Susan B Bressman, Laurie J Ozelius, José C Cabassa, Rachel Saunders-Pullman

    NPJ Parkinson's disease　9　(1)　160-160　2023/12/07

    DOI： 10.1038/s41531-023-00599-6 　

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    There is a paucity of genetic characterization in people with Parkinson's disease (PD) of Latino and Afro-Caribbean descent. Screening LRRK2 and GBA variants in 32 New Yorkers of Puerto Rican ethnicity with PD and in 119 non-Hispanic-non-Jewish European PD cases revealed that Puerto Rican participants were more likely to harbor the LRRK2-p.G2019S variant (15.6% vs. 4.2%, respectively). Additionally, whole exome sequencing of twelve Puerto Rican and Dominican PD participants was performed as an exploratory study.

  9. LONRF2 is a protein quality control ubiquitin ligase whose deficiency causes late-onset neurological deficits. International-journal

    Dan Li, Yoshikazu Johmura, Satoru Morimoto, Miyuki Doi, Keiko Nakanishi, Manabu Ozawa, Yuji Tsunekawa, Akane Inoue-Yamauchi, Hiroya Naruse, Takashi Matsukawa, Yukio Takeshita, Naoki Suzuki, Masashi Aoki, Ayumi Nishiyama, Xin Zeng, Chieko Konishi, Narumi Suzuki, Atsuya Nishiyama, Alexander Stephen Harris, Mariko Morita, Kiyoshi Yamaguchi, Yoichi Furukawa, Kenta Nakai, Shoji Tsuji, Satoshi Yamazaki, Yuji Yamanashi, Shoichi Shimada, Takashi Okada, Hideyuki Okano, Tatsushi Toda, Makoto Nakanishi

    Nature aging　3　(8)　1001-1019　2023/07/20

    DOI： 10.1038/s43587-023-00464-4 　

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    Protein misfolding is a major factor of neurodegenerative diseases. Post-mitotic neurons are highly susceptible to protein aggregates that are not diluted by mitosis. Therefore, post-mitotic cells may have a specific protein quality control system. Here, we show that LONRF2 is a bona fide protein quality control ubiquitin ligase induced in post-mitotic senescent cells. Under unperturbed conditions, LONRF2 is predominantly expressed in neurons. LONRF2 binds and ubiquitylates abnormally structured TDP-43 and hnRNP M1 and artificially misfolded proteins. Lonrf2-/- mice exhibit age-dependent TDP-43-mediated motor neuron (MN) degeneration and cerebellar ataxia. Mouse induced pluripotent stem cell-derived MNs lacking LONRF2 showed reduced survival, shortening of neurites and accumulation of pTDP-43 and G3BP1 after long-term culture. The shortening of neurites in MNs from patients with amyotrophic lateral sclerosis is rescued by ectopic expression of LONRF2. Our findings reveal that LONRF2 is a protein quality control ligase whose loss may contribute to MN degeneration and motor deficits.

  10. CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis. International-journal Peer-reviewed

    Kodai Kume, Takashi Kurashige, Keiko Muguruma, Hiroyuki Morino, Yui Tada, Mai Kikumoto, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Yukiko Matsuda, Shinya Matsuura, Masahiro Nakamori, Ayumi Nishiyama, Rumiko Izumi, Tetsuya Niihori, Masashi Ogasawara, Nobuyuki Eura, Tamaki Kato, Mamoru Yokomura, Yoshiaki Nakayama, Hidefumi Ito, Masataka Nakamura, Kayoko Saito, Yuichi Riku, Yasushi Iwasaki, Hirofumi Maruyama, Yoko Aoki, Ichizo Nishino, Yuishin Izumi, Masashi Aoki, Hideshi Kawakami

    American journal of human genetics　110　(7)　1086-1097　2023/06/20

    DOI： 10.1016/j.ajhg.2023.05.014 　

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    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.

  11. Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. International-journal

    Satoru Morimoto, Shinichi Takahashi, Daisuke Ito, Yugaku Daté, Kensuke Okada, Chris Kato, Shiho Nakamura, Fumiko Ozawa, Chai Muh Chyi, Ayumi Nishiyama, Naoki Suzuki, Koki Fujimori, Tosho Kondo, Masaki Takao, Miwa Hirai, Yasuaki Kabe, Makoto Suematsu, Masahiro Jinzaki, Masashi Aoki, Yuto Fujiki, Yasunori Sato, Norihiro Suzuki, Jin Nakahara, Hideyuki Okano

    Cell stem cell　30　(6)　766-780　2023/06/01

    DOI： 10.1016/j.stem.2023.04.017 　

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    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.

  12. 【ALS-どこまでわかり,どこまで治るか】原因と発症機序 SOD1

    青木 正志, 西山 亜由美, 割田 仁

    Clinical Neuroscience　41　(3)　334-337　2023/03

    Publisher: (株)中外医学社

    ISSN： 0289-0585

  13. 大規模レジストリデータベース(PRO-ACT)を活用したALSに対するロピニロール塩酸塩の有効性の検証

    森本 悟, 高橋 愼一, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chai Muh Chy, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    神経治療学　39　(6)　S257-S257　2022/10

    Publisher: (一社)日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  14. 大規模レジストリデータベースを活用したALS治験(ROPALS試験)におけるロピニロール塩酸塩の有効性の検証

    高橋 愼一, 森本 悟, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chyi Muh Chai, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    脳循環代謝　34　(1)　142-142　2022/10

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  15. 大規模レジストリデータベース(PRO-ACT)を活用したALSに対するロピニロール塩酸塩の有効性の検証

    森本 悟, 高橋 愼一, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chai Muh Chy, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    神経治療学　39　(6)　S257-S257　2022/10

    Publisher: (一社)日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  16. Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy. International-journal

    Naoki Suzuki, Ayumi Nishiyama, Hitoshi Warita, Masashi Aoki

    Journal of human genetics　2022/06/13

    DOI： 10.1038/s10038-022-01055-8 　

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    Amyotrophic lateral sclerosis (ALS) is an intractable disease that causes respiratory failure leading to mortality. The main locus of ALS is motor neurons. The success of antisense oligonucleotide (ASO) therapy in spinal muscular atrophy (SMA), a motor neuron disease, has triggered a paradigm shift in developing ALS therapies. The causative genes of ALS and disease-modifying genes, including those of sporadic ALS, have been identified one after another. Thus, the freedom of target choice for gene therapy has expanded by ASO strategy, leading to new avenues for therapeutic development. Tofersen for superoxide dismutase 1 (SOD1) was a pioneer in developing ASO for ALS. Improving protocols and devising early interventions for the disease are vital. In this review, we updated the knowledge of causative genes in ALS. We summarized the genetic mutations identified in familial ALS and their clinical features, focusing on SOD1, fused in sarcoma (FUS), and transacting response DNA-binding protein. The frequency of the C9ORF72 mutation is low in Japan, unlike in Europe and the United States, while SOD1 and FUS are more common, indicating that the target mutations for gene therapy vary by ethnicity. A genome-wide association study has revealed disease-modifying genes, which could be the novel target of gene therapy. The current status and prospects of gene therapy development were discussed, including ethical issues. Furthermore, we discussed the potential of axonal pathology as new therapeutic targets of ALS from the perspective of early intervention, including intra-axonal transcription factors, neuromuscular junction disconnection, dysregulated local translation, abnormal protein degradation, mitochondrial pathology, impaired axonal transport, aberrant cytoskeleton, and axon branching. We simultaneously discuss important pathological states of cell bodies: persistent stress granules, disrupted nucleocytoplasmic transport, and cryptic splicing. The development of gene therapy based on the elucidation of disease-modifying genes and early intervention in molecular pathology is expected to become an important therapeutic strategy in ALS.

  17. ALSに対するロピニロール塩酸塩に関するランダム化臨床試験の結果(ROPALS)(Results Of A Randomized Clinical Trial of Ropinirole Hydrochloride For ALS(ROPALS))

    高橋 愼一, 森本 悟, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chai Muh Chyi, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    脳循環代謝　33　(1)　129-129　2021/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  18. iPS細胞創薬に基づいた筋萎縮性側索硬化症(ALS)に対するロピニロール塩酸塩の医師主導治験(ROPALS試験)

    森本 悟, 高橋 愼一, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chai Muh Chyi, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    神経治療学　38　(6)　S261-S261　2021/10

    Publisher: (一社)日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  19. Reduced PHOX2B stability causes axonal growth impairment in motor neurons with TARDBP mutations. International-journal

    Shio Mitsuzawa, Naoki Suzuki, Tetsuya Akiyama, Mitsuru Ishikawa, Takefumi Sone, Jiro Kawada, Ryo Funayama, Matsuyuki Shirota, Hiroaki Mitsuhashi, Satoru Morimoto, Kensuke Ikeda, Tomomi Shijo, Akiyuki Ohno, Naoko Nakamura, Hiroya Ono, Risako Ono, Shion Osana, Tadashi Nakagawa, Ayumi Nishiyama, Rumiko Izumi, Shohei Kaneda, Yoshiho Ikeuchi, Keiko Nakayama, Teruo Fujii, Hitoshi Warita, Hideyuki Okano, Masashi Aoki

    Stem cell reports　16　(6)　1527-1541　2021/06/08

    DOI： 10.1016/j.stemcr.2021.04.021 　

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    Amyotrophic lateral sclerosis (ALS) is an adult-onset incurable motor neuron (MN) disease. The reasons for selective MN vulnerability in ALS are unknown. Axonal pathology is among the earliest signs of ALS. We searched for novel modulatory genes in human MN axon shortening affected by TARDBP mutations. In transcriptome analysis of RNA present in the axon compartment of human-derived induced pluripotent stem cell (iPSC)-derived MNs, PHOX2B (paired-like homeobox protein 2B) showed lower expression in TARDBP mutant axons, which was consistent with axon qPCR and in situ hybridization. PHOX2B mRNA stability was reduced in TARDBP mutant MNs. Furthermore, PHOX2B knockdown reduced neurite length in human MNs. Finally, phox2b knockdown in zebrafish induced short spinal axons and impaired escape response. PHOX2B is known to be highly express in other types of neurons maintained after ALS progression. Collectively, TARDBP mutations induced loss of axonal resilience, which is an important ALS-related phenotype mediated by PHOX2B downregulation.

  20. Possible Somatic Mosaicism of Novel FUS Variant in Familial Amyotrophic Lateral Sclerosis. International-journal

    Shin Hisahara, Ayumi Nishiyama, Emiko Tsuda, Syuuichirou Suzuki, Akihiro Matsumura, Aki Ishikawa, Akihiro Sakurai, Ikuko N Motoike, Masashi Aoki, Yoko Aoki, Shun Shimohama

    Neurology. Genetics　7　(1)　e552　2021/02

    DOI： 10.1212/NXG.0000000000000552 　

  21. 異なる臨床病型を呈し母にFUS遺伝子変異のmosaicismが示唆された家族性ALSの親子例

    久原 真, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 石川 亜貴, 櫻井 晃洋, 西山 亜由美, 元池 育子, 青木 正志, 青木 洋子, 下濱 俊

    臨床神経学　61　(1)　55-55　2021/01

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  22. A case of inflammatory myopathy with anti-PM/Scl antibodies myopathologically presenting as polymyositis with mitochondrial pathology

    Arifumi Matsumoto, Rumiko Izumi, Naoto Sugeno, Naoki Suzuki, Chihiro Namatame, Temma Soga, Ayumi Nishiyama, Hiroshi Kuroda, Masashi Aoki, Isao Nagano

    NEUROLOGY AND CLINICAL NEUROSCIENCE　8　(5)　335-339　2020/09

    DOI： 10.1111/ncn3.12429 　

    ISSN： 2049-4173

  23. Facial onset amyotrophic lateral sclerosis with K3E variant in the Cu/Zn superoxide dismutase gene. International-journal

    Kazumoto Shibuya, Setsu Sawai, Atsuhiko Sugiyama, Mizuho Koide, Ayumi Nishiyama, Masashi Aoki, Satoshi Kuwabara

    Amyotrophic lateral sclerosis & frontotemporal degeneration　22　(1-2)　1-3　2020/07/30

    DOI： 10.1080/21678421.2020.1797092 　

    More details Close

    We describe a 48-year-old man, suffering from difficulties in closing his eyes. He subsequently experienced progressive weakness in the facial and bulbar regions and upper limbs. His father and paternal grandmother had limb weakness as initial manifestations and were diagnosed with amyotrophic lateral sclerosis (ALS). In the present case, neuroimaging and laboratory studies were unremarkable, and neurophysiological studies disclosed diffuse denervation. Genetic testing identified a heterozygous c.10A>G, p.K4E (K3E) variant in superoxide dismutase 1 (SOD1) gene, and he was diagnosed with familial ALS. In ALS, facial muscles are rarely involved as an initial symptom. The present patient is a first case of facial onset ALS with K3E variant in SOD1 gene. Two case reports identified facial palsy as an initial manifestation in familial ALS with C6G variant in SOD1 gene. Several ALS patients with variants in SOD1 gene may have facial onset history.

  24. Generation of an ALS human iPSC line KEIOi001-A from peripheral blood of a Charcot disease-affected patient carrying TARDBP p.N345K heterozygous SNP mutation. International-journal Peer-reviewed

    Nicolas Leventoux, Satoru Morimoto, Kenju Hara, Shiho Nakamura, Fumiko Ozawa, Shio Mitsuzawa, Tetsuya Akiyama, Ayumi Nishiyama, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Hideyuki Okano

    Stem cell research　47　101896-101896　2020/06/28

    DOI： 10.1016/j.scr.2020.101896 　

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    Amyotrophic Lateral Sclerosis is the most common motor neuron degenerative disease in adults, and TARDBP gene mutations have been reported to be involved in the pathogenesis. We present here how we generated the human induced pluripotent stem cell (hiPSC) line KEIOi001-A/SM4-4-5 from the peripheral blood of a 63-year-old male patient presenting the c.1035C > G heterozygous SNP mutation in the TARDBP gene locus. The established hiPSC line does not express the exogenous reprogramming factors oriP nor EBNA1 and shows no karyotypic abnormalities, while it expresses pluripotent stem cell markers, presents the SNP mutation and is capable of three-germ layers differentiation in vitro.

  25. 頭部外傷を契機に発症した抗MOG抗体関連脳脊髄炎の一例

    佐藤 一輝, 西山 亜由美, 鈴木 直輝, 張替 宗介, 齋藤 早紀, 池田 謙輔, 西山 修平, 三須 建郎, 割田 仁, 黒田 宙, 青木 正志

    臨床神経学　59　(11)　760-760　2019/11

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  26. p.N345K mutation in TARDBP in a patient with familial amyotrophic lateral sclerosis: An autopsy case. International-journal Peer-reviewed

    Takahiro Takeda, Mutsumi Iijima, Yuko Shimizu, Hiroshi Yoshizawa, Mayu Miyashiro, Hiromi Onizuka, Tomoko Yamamoto, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Noriyuki Shibata, Kazuo Kitagawa

    Neuropathology : official journal of the Japanese Society of Neuropathology　39　(4)　286-293　2019/08

    DOI： 10.1111/neup.12559 　

    ISSN： 0919-6544

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    We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA-binding protein 43 kDa (TDP-43) gene (TARDBP). A 62-year-old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron signs and lower motor neuron involvement corroborated by needle electromyography. The patient was diagnosed as having probable ALS according to the revised El Escorial diagnostic criteria and was eventually diagnosed with familial ALS. At 65 years of age, respiratory failure became critical, and artificial ventilation was initiated. At 70 years of age, the patient died from a urinary tract infection. Histopathological investigation showed Bunina bodies in the remaining motor neurons and anterolateral funicular myelin pallor in the spinal cord. TDP-43-positive cytoplasmic inclusions were quite rare in the spinal cord motor neurons, being predominantly present in the glial cells (especially astrocytes) of the spinal cord anterior horn. Although the reason for the preferential vulnerability of spinal glial cells to TARDBP mutations remains unclear, our findings indicate that TARDBP p.N345K mutation could have an influence on the topography of TDP-43 aggregation.

  27. 肺癌術後に発症し、治療に難渋した傍腫瘍性NMOSDの1例

    松原 史歩, 西山 修平, 中屋 亮彦, 小野 理佐子, 西山 亜由美, 三須 建郎, 割田 仁, 黒田 宙, 青木 正志

    臨床神経学　59　(7)　477-477　2019/07

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  28. Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons. International-journal Peer-reviewed

    Tetsuya Akiyama, Naoki Suzuki, Mitsuru Ishikawa, Koki Fujimori, Takefumi Sone, Jiro Kawada, Ryo Funayama, Fumiyoshi Fujishima, Shio Mitsuzawa, Kensuke Ikeda, Hiroya Ono, Tomomi Shijo, Shion Osana, Matsuyuki Shirota, Tadashi Nakagawa, Yasuo Kitajima, Ayumi Nishiyama, Rumiko Izumi, Satoru Morimoto, Yohei Okada, Takayuki Kamei, Mayumi Nishida, Masahiro Nogami, Shohei Kaneda, Yoshiho Ikeuchi, Hiroaki Mitsuhashi, Keiko Nakayama, Teruo Fujii, Hitoshi Warita, Hideyuki Okano, Masashi Aoki

    EBioMedicine　45　362-378　2019/07

    DOI： 10.1016/j.ebiom.2019.06.013 　

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    BACKGROUND: The characteristic structure of motor neurons (MNs), particularly of the long axons, becomes damaged in the early stages of amyotrophic lateral sclerosis (ALS). However, the molecular pathophysiology of axonal degeneration remains to be fully elucidated. METHOD: Two sets of isogenic human-induced pluripotent stem cell (hiPSCs)-derived MNs possessing the single amino acid difference (p.H517D) in the fused in sarcoma (FUS) were constructed. By combining MN reporter lentivirus, MN specific phenotype was analyzed. Moreover, RNA profiling of isolated axons were conducted by applying the microfluidic devices that enable axon bundles to be produced for omics analysis. The relationship between the target gene, which was identified as a pathological candidate in ALS with RNA-sequencing, and the MN phenotype was confirmed by intervention with si-RNA or overexpression to hiPSCs-derived MNs and even in vivo. The commonality was further confirmed with other ALS-causative mutant hiPSCs-derived MNs and human pathology. FINDINGS: We identified aberrant increasing of axon branchings in FUS-mutant hiPSCs-derived MN axons compared with isogenic controls as a novel phenotype. We identified increased level of Fos-B mRNA, the binding target of FUS, in FUS-mutant MNs. While Fos-B reduction using si-RNA or an inhibitor ameliorated the observed aberrant axon branching, Fos-B overexpression resulted in aberrant axon branching even in vivo. The commonality of those phenotypes was further confirmed with other ALS causative mutation than FUS. INTERPRETATION: Analyzing the axonal fraction of hiPSC-derived MNs using microfluidic devices revealed that Fos-B is a key regulator of FUS-mutant axon branching. FUND: Japan Agency for Medical Research and development; Japanese Ministry of Education, Culture, Sports, Science and Technology Clinical Research, Innovation and Education Center, Tohoku University Hospital; Japan Intractable Diseases (Nanbyo) Research Foundation; the Kanae Foundation for the Promotion of Medical Science; and "Inochi-no-Iro" ALS research grant.

  29. A case of neuralgic amyotrophy presented Vernet syndrome and suprascapular nerve palsy Peer-reviewed

    Iino Akira, Sugeno Naoto, Namatame Chihiro, Nishiyama Ayumi, Kuroda Hiroshi, Misu Tatsuro, Aoki Masashi

    NEUROLOGY AND CLINICAL NEUROSCIENCE　7　(3)　127-128　2019/05

    DOI： 10.1111/ncn3.12264 　

    ISSN： 2049-4173

  30. Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis. International-journal Peer-reviewed

    Tomomi Shijo, Hitoshi Warita, Naoki Suzuki, Kensuke Ikeda, Shio Mitsuzawa, Tetsuya Akiyama, Hiroya Ono, Ayumi Nishiyama, Rumiko Izumi, Yasuo Kitajima, Masashi Aoki

    Experimental neurology　307　164-179　2018/09

    DOI： 10.1016/j.expneurol.2018.06.009 　

    ISSN： 0014-4886

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    Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterized by the systemic loss of motor neurons with prominent astrocytosis and microgliosis in the spinal cord and brain. Astrocytes play an essential role in maintaining extracellular microenvironments that surround motor neurons, and are activated by various insults. Growing evidence points to a non-cell autonomous neurotoxicity caused by chronic and sustained astrocytic activation in patients with neurodegenerative diseases, including ALS. However, the mechanisms that underlie the harmful effects of astrocytosis in patients with ALS remain unresolved. We focused on bone morphogenetic proteins as a major soluble factor that promotes astrocytogenesis and its activation in the adult spinal cord. In a transgenic rat model with ALS-linked mutant Cu/Zn superoxide dismutase gene, BMP4 was progressively up-regulated in reactive astrocytes of the spinal ventral horns, whereas the BMP-antagonist noggin was decreased in association with neuronal degeneration. Continuous intrathecal noggin supplementation after disease onset significantly ameliorated motor dysfunction symptoms, neurogenic muscle atrophy, and extended survival of symptomatic ALS model rats, despite lack of deterrence against neuronal death itself. The exogenous noggin inhibited astrocytic hypertrophy, astrocytogenesis, and neuroinflammation by inactivating both Smad1/5/8 and p38 mitogen-activated protein kinase pathways. Moreover, intrathecal infusion of a Bmp4-targeted antisense oligonucleotides and provided selective Bmp4 knockdown in vivo, which suppressed astrocyte and microglia activation, reproducing the aforementioned results by noggin treatment. Collectively, we clarified the involvement of BMP4 in the processes of excessive gliosis that exacerbate the disease progression of the ALS model rats. Our study demonstrated that BMP4, with its downstream signaling, might be a novel therapeutic target for disease-modifying therapies in ALS.

  31. 下位脳神経障害を伴った神経痛性筋萎縮症の1例

    生田目 知尋, 西山 亜由美, 菅野 直人, 黒田 宙, 三須 建郎, 青木 正志

    臨床神経学　58　(8)　536-536　2018/08

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  32. TARDBP p.G376D mutation, found in rapid progressive familial ALS, induces mislocalization of TDP-43. International-journal Peer-reviewed

    Shio Mitsuzawa, Tetsuya Akiyama, Ayumi Nishiyama, Naoki Suzuki, Masaaki Kato, Hitoshi Warita, Rumiko Izumi, Shion Osana, Shingo Koyama, Takeo Kato, Yoshihiro Suzuki, Masashi Aoki

    eNeurologicalSci　11　20-22　2018/06

    DOI： 10.1016/j.ensci.2018.04.001 　

  33. 長期経過中に敗血症で死亡した家族性広汎型筋萎縮性側索硬化症の一剖検例

    宮代 麻由, 鬼塚 裕美, 武田 貴裕, 山本 智子, 鈴木 直輝, 西山 亜由美, 青木 正志, 北川 一夫, 柴田 亮行

    日本病理学会会誌　107　(1)　532-532　2018/04

    Publisher: (一社)日本病理学会

    ISSN： 0300-9181

  34. Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a rat model of amyotrophic lateral sclerosis. International-journal Peer-reviewed

    Tomomi Shijo, Hitoshi Warita, Naoki Suzuki, Yasuo Kitajima, Kensuke Ikeda, Tetsuya Akiyama, Hiroya Ono, Shio Mitsuzawa, Ayumi Nishiyama, Rumiko Izumi, Masashi Aoki

    Journal of neuroscience research　96　(2)　222-233　2018/02

    DOI： 10.1002/jnr.24127 　

    ISSN： 0360-4012

    eISSN： 1097-4547

  35. Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis. International-journal Peer-reviewed

    Ayumi Nishiyama, Tetsuya Niihori, Hitoshi Warita, Rumiko Izumi, Tetsuya Akiyama, Masaaki Kato, Naoki Suzuki, Yoko Aoki, Masashi Aoki

    Neurobiology of aging　53　194.e1-194.e8-194.e8　2017/05

    DOI： 10.1016/j.neurobiolaging.2017.01.004 　

    ISSN： 0197-4580

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    Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 patients with familial ALS (45 pedigrees), we performed targeted next-generation sequencing of 35 known ALS/motor neuron diseases-related genes. Known variants in ANG, OPTN, SETX, and TARDBP were identified in 6 patients. A novel likely pathogenic homozygous variant in ALS2 was identified in 1 patient. In addition, 18 patients harbored 1-3 novel variants of uncertain significance, whereas hexanucleotide repeat expansions in C9ORF72 were not detected using repeat-primed polymerase chain reaction. Collectively, in our Japanese cohort, the frequencies of SOD1, FUS, SETX, TARDBP, ANG, and OPTN variants were 32%, 11%, 2%, 2%, 1%, and 1%, respectively. These findings indicate considerable differences in the genetic variations associated with familial ALS across populations. Further genetic analyses and functional studies of novel variants are warranted.

  36. Prominent sensory involvement in a case of familial amyotrophic lateral sclerosis carrying the L8V SOD1 mutation. International-journal Peer-reviewed

    Ayumi Nishiyama, Hitoshi Warita, Toshiaki Takahashi, Naoki Suzuki, Shuhei Nishiyama, Ohito Tano, Tetsuya Akiyama, Yasuaki Watanabe, Kenta Takahashi, Hiroshi Kuroda, Masaaki Kato, Maki Tateyama, Tetsuya Niihori, Yoko Aoki, Masashi Aoki

    Clinical neurology and neurosurgery　150　194-196　2016/11

    DOI： 10.1016/j.clineuro.2016.08.008 　

    ISSN： 0303-8467

  37. Genotype-phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan. International-journal Peer-reviewed

    Tetsuya Akiyama, Hitoshi Warita, Masaaki Kato, Ayumi Nishiyama, Rumiko Izumi, Chikako Ikeda, Masaki Kamada, Naoki Suzuki, Masashi Aoki

    Muscle & nerve　54　(3)　398-404　2016/09

    DOI： 10.1002/mus.25061 　

    ISSN： 0148-639X

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    INTRODUCTION: We investigated possible genotype-phenotype correlations in Japanese patients with familial amyotrophic lateral sclerosis (FALS) carrying fused in sarcoma/translated in liposarcoma (FUS/TLS) gene mutations. METHODS: A consecutive series of 111 Japanese FALS pedigrees were screened for copper/zinc superoxide dismutase 1 (SOD1) and FUS/TLS gene mutations. Clinical data, including onset age, onset site, disease duration, and extramotor symptoms, were collected. RESULTS: Nine different FUS/TLS mutations were found in 12 pedigrees. Most of the patients with FUS/TLS-linked FALS demonstrated early onset in the brainstem/upper cervical region, and relatively short disease duration. A few mutations exhibited phenotypes that were distinct from typical cases. Frontotemporal dementia was present in 1 patient. CONCLUSIONS: This study revealed a characteristic phenotype in FUS/TLS-linked FALS patients in Japan. FUS/TLS screening is recommended in patients with FALS with this phenotype. Muscle Nerve 54: 398-404, 2016.

  38. Isolated inclusion body myopathy caused by a multisystem proteinopathy-linked hnRNPA1 mutation. International-journal Peer-reviewed

    Rumiko Izumi, Hitoshi Warita, Tetsuya Niihori, Toshiaki Takahashi, Maki Tateyama, Naoki Suzuki, Ayumi Nishiyama, Matsuyuki Shirota, Ryo Funayama, Keiko Nakayama, Satomi Mitsuhashi, Ichizo Nishino, Yoko Aoki, Masashi Aoki

    Neurology. Genetics　1　(3)　e23　2015/10

    DOI： 10.1212/NXG.0000000000000023 　

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    OBJECTIVE: To identify the genetic cause of isolated inclusion body myopathy (IBM) with autosomal dominant inheritance in 2 families. METHODS: Genetic investigations were performed using whole-exome and Sanger sequencing of the heterogeneous nuclear ribonucleoprotein A1 gene (hnRNPA1). The clinical and pathologic features of patients in the 2 families were evaluated with neurologic examinations, muscle imaging, and muscle biopsy. RESULTS: We identified a missense p.D314N mutation in hnRNPA1, which is also known to cause familial amyotrophic lateral sclerosis, in 2 families with IBM. The affected individuals developed muscle weakness in their 40s, which slowly progressed toward a limb-girdle pattern. Further evaluation of the affected individuals revealed no apparent motor neuron dysfunction, cognitive impairment, or bone abnormality. The muscle pathology was compatible with IBM, lacking apparent neurogenic change and inflammation. Multiple immunohistochemical analyses revealed the cytoplasmic aggregation of hnRNPA1 in close association with autophagosomes and myonuclei. Furthermore, the aberrant accumulation was characterized by coaggregation with ubiquitin, sequestome-1/p62, valosin-containing protein/p97, and a variety of RNA-binding proteins (RBPs). CONCLUSIONS: The present study expands the clinical phenotype of hnRNPA1-linked multisystem proteinopathy. Mutations in hnRNPA1, and possibly hnRNPA2B1, will be responsible for isolated IBM with a pure muscular phenotype. Although the mechanisms underlying the selective skeletal muscle involvement remain to be elucidated, the immunohistochemical results suggest a broad sequestration of RBPs by the mutated hnRNPA1.

  39. GNE myopathy associated with congenital thrombocytopenia: a report of two siblings. International-journal Peer-reviewed

    Rumiko Izumi, Tetsuya Niihori, Naoki Suzuki, Yoji Sasahara, Takeshi Rikiishi, Ayumi Nishiyama, Shuhei Nishiyama, Kaoru Endo, Masaaki Kato, Hitoshi Warita, Hidehiko Konno, Toshiaki Takahashi, Maki Tateyama, Takeshi Nagashima, Ryo Funayama, Keiko Nakayama, Shigeo Kure, Yoichi Matsubara, Yoko Aoki, Masashi Aoki

    Neuromuscular disorders : NMD　24　(12)　1068-72　2014/12

    DOI： 10.1016/j.nmd.2014.07.008 　

    ISSN： 0960-8966

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    GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia.

  40. A Case Series of Longitudinally Extended Transverse Myelitis with Increased Polymorphonuclear Leukocytes in CSF Peer-reviewed

    Kuroda Hiroshi, Takahashi Toshiyuki, Sato Douglas Kazutoshi, Nishiyama Ayumi, Miura Emiko, Nishiyama Shuhei, Sugeno Naoto, Misu Tatsuro, Nakashima Ichiro, Fujihara Kazuo, Aoki Masashi

    MULTIPLE SCLEROSIS JOURNAL　20　(7)　953　2014/06

    ISSN： 1352-4585

  41. Postural leg tremor in X-linked spinal and bulbar muscular atrophy. International-journal Peer-reviewed

    Ayumi Nishiyama, Naoto Sugeno, Maki Tateyama, Shuhei Nishiyama, Masaaki Kato, Masashi Aoki

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia　21　(5)　799-802　2014/05

    DOI： 10.1016/j.jocn.2013.07.026 　

    ISSN： 0967-5868

    eISSN： 1532-2653

  42. A case of steroid-responsive MADSAM with late appearance of a partial conduction block in the forearm. International-journal Peer-reviewed

    Shun Yoshida, Akio Kikuchi, Maki Tateyama, Ohito Tano, Ayumi Nishiyama, Tetsuya Akaishi, Masaaki Kato, Masashi Aoki

    Journal of neurology　261　(4)　825-7　2014/04

    DOI： 10.1007/s00415-014-7271-5 　

    ISSN： 0340-5354

    eISSN： 1432-1459

  43. Corticospinal tract signal changes in a patient with spinal and bulbar muscular atrophy Peer-reviewed

    Naoto Sugeno, Ayumu Sunaguchi, Ayumi Nishiyama, Masaaki Kato, Masashi Aoki

    Neurology and Clinical Neuroscience　1　(3)　125　2013/05

    DOI： 10.1111/j.2049-4173.2013.00025.x 　

Show all ︎Show first 5

Misc. 51

  1. ALS遺伝子治療の最前線-課題と未来への展望 遺伝子治療時代に向けた迅速遺伝子診断の体制構築

    西山 亜由美, 鈴木 直輝, 青木 正志

    神経治療学　42　(6)　S130-S130　2025/10

    Publisher: (一社)日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  2. ALS遺伝子治療の最前線-課題と未来への展望 遺伝子治療時代に向けた迅速遺伝子診断の体制構築

    西山 亜由美, 鈴木 直輝, 青木 正志

    神経治療学　42　(6)　S130-S130　2025/10

    Publisher: (一社)日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  3. 筋萎縮性側索硬化症患者における横隔神経複合筋活動電位の縦断的検討

    四條 友望, 鈴木 直輝, 浅黄 優, 池田 謙輔, 西山 亜由美, 光澤 志緒, 加藤 昌昭, 割田 仁, 中里 信和, 青木 正志

    臨床神経学　65　(Suppl.)　S235-S235　2025/09

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  4. 遺伝子治療時代に向けた迅速遺伝子診断の体制構築

    西山亜由美, 鈴木直輝, 青木正志

    神経治療学(Web)　42　(6)　2025

    ISSN： 2189-7824

  5. 神経変性疾患領域における難病の医療水準の向上や患者のQOL向上に資する研究 本邦の家族性ALSの臨床像と遺伝学的背景

    青木正志, 西山亜由美, 鈴木直輝, 割田仁, 池田謙輔

    神経変性疾患領域における難病の医療水準の向上や患者のQOL向上に資する研究 令和5年度 総括・分担研究報告書(Web)　2024

  6. 大規模レジストリデータベースを活用したALS治験(ROPALS試験)におけるロピニロール塩酸塩の有効性の検証

    高橋 愼一, 森本 悟, 伊東 大介, 伊達 悠岳, 岡田 健佑, Chyi Muh Chai, 西山 亜由美, 鈴木 直輝, 平井 美和, 加部 泰明, 末松 誠, 陣崎 雅弘, 青木 正志, 佐藤 泰憲, 中原 仁, 鈴木 則宏, 岡野 栄之

    脳循環代謝　34　(1)　142-142　2022/10

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  7. 大規模レジストリデータベース(PRO-ACT)を活用したALSに対するロピニロール塩酸塩の有効性の検証

    森本悟, 森本悟, 高橋愼一, 高橋愼一, 高橋愼一, 伊東大介, 伊東大介, 伊達悠岳, 岡田健佑, CHAI Muh Chy, CHAI Muh Chy, 西山亜由美, 鈴木直輝, 平井美和, 加部泰明, 末松誠, 陣崎雅弘, 青木正志, 佐藤泰憲, 中原仁, 鈴木則宏, 岡野栄之

    神経治療学(Web)　39　(6)　2022

    ISSN： 2189-7824

  8. 大規模レジストリデータベースを活用したALS治験(ROPALS試験)におけるロピニロール塩酸塩の有効性の検証

    高橋愼一, 高橋愼一, 高橋愼一, 森本悟, 森本悟, 伊東大介, 伊東大介, 伊達悠岳, 岡田健佑, CHAI Muh Chyi, CHAI Muh Chyi, 西山亜由美, 鈴木直輝, 平井美和, 加部泰明, 末松誠, 陣崎雅弘, 青木正志, 佐藤泰憲, 中原仁, 鈴木則宏, 岡野栄之

    脳循環代謝(Web)　34　(1)　2022

    ISSN： 2188-7519

  9. 【神経疾患を克服する-わが国の戦略(1)】研究手法の最新の話題 遺伝子・ゲノム医療

    青木 正志, 西山 亜由美

    Clinical Neuroscience　39　(9)　1103-1108　2021/09

    Publisher: (株)中外医学社

    ISSN： 0289-0585

  10. 臨床病型が大きく異なりFUS遺伝子変異のmosaicismが示唆された家族性ALS母子例

    久原 真, 西山 亜由美, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 石川 亜貴, 櫻井 晃洋, 元池 育子, 青木 正志, 青木 洋子, 下濱 俊

    臨床神経学　61　(Suppl.)　S293-S293　2021/09

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  11. Results Of A Randomized Clinical Trial of Ropinirole Hydrochloride For ALS (ROPALS)

    高橋愼一, 高橋愼一, 高橋愼一, 森本悟, 森本悟, 伊東大介, 伊達悠岳, 岡田健佑, CHAI Muh Chyi, 西山亜由美, 鈴木直輝, 平井美和, 加部泰明, 末松誠, 陣崎雅弘, 青木正志, 佐藤泰憲, 中原仁, 鈴木則宏, 岡野栄之

    脳循環代謝(Web)　33　(1)　2021

    ISSN： 2188-7519

  12. 多系統蛋白質症(MSP)患者の全国実態調査と診療体制構築に関する研究 HNRNPA1変異を伴う多系統蛋白質症(MSP3型)新規家系の同定

    青木正志, 割田仁, 井泉瑠美子, 井泉瑠美子, 池田謙輔, 鈴木直輝, 高橋俊明, 竪山真規, 西山亜由美, 城田松之, 舟山亮, 中山啓子, 三橋里美, 西野一三, 新堀哲也, 青木洋子

    多系統蛋白質症(MSP)患者の全国実態調査と診療体制構築に関する研究 令和2年度 総括・分担研究報告書(Web)　2021

  13. iPS細胞創薬に基づいた筋萎縮性側索硬化症(ALS)に対するロピニロール塩酸塩の医師主導治験(ROPALS試験)

    森本悟, 森本悟, 高橋愼一, 高橋愼一, 高橋愼一, 伊東大介, 伊達悠岳, 岡田健佑, CHAI Muh Chyi, CHAI Muh Chyi, 西山亜由美, 鈴木直輝, 平井美和, 加部泰明, 末松誠, 陣崎雅弘, 青木正志, 佐藤泰憲, 中原仁, 鈴木則宏, 岡野栄之

    神経治療学(Web)　38　(6)　2021

    ISSN： 2189-7824

  14. 頭部外傷を契機に発症した抗MOG抗体関連脳脊髄炎の一例

    佐藤 一輝, 西山 亜由美, 鈴木 直輝, 張替 宗介, 齋藤 早紀, 池田 謙輔, 西山 修平, 三須 建郎, 割田 仁, 黒田 宙, 青木 正志

    臨床神経学　59　(11)　760-760　2019/11

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  15. [Familial Amyotrophic Lateral Sclerosis].

    Naoki Suzuki, Ayumi Nishiyama, Masaaki Kato, Hitoshi Warita, Masashi Aoki

    Brain and nerve = Shinkei kenkyu no shinpo　71　(11)　1169-1181　2019/11

    DOI： 10.11477/mf.1416201427 　

    More details Close

    Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. Riluzole and edaravone are the only approved drugs available in Japan to date. Approximately 10% of ALS cases are familial in rature, defined as the existence of disease-causing mutation. SOD1 is the most frequent causative gene for ALS among Japanese individuals, while C9orf72 mutation is more prevalent in Western countries. Genotype-phenotype correlation described in the literature of familial ALS enables to establish models of the disease. This review article describes the clinical characteristics of familial ALS based on each disease-causing mutation. The pathomechanism of ALS including proteostasis, RNA metabolism, and axonal pathology are discussed in detail. We also reviewed the status of development of therapeutic strategies for familial ALS based on analysis of animal models and induced pluripotent stem cells.

  16. 【ALS 2019】家族性ALS

    鈴木 直輝, 西山 亜由美, 加藤 昌昭, 割田 仁, 青木 正志

    BRAIN and NERVE: 神経研究の進歩　71　(11)　1169-1181　2019/11

    Publisher: (株)医学書院

    ISSN： 1881-6096

    eISSN： 1344-8129

  17. 多系統蛋白質症(MSP)の疾患概念確立および診断基準作成,診療体制構築に関する研究 hnRNPA1変異を伴う多系統蛋白質症(MSP)3型の新規家系探索

    青木正志, 割田仁, 井泉瑠美子, 井泉瑠美子, 池田謙輔, 鈴木直輝, 高橋俊明, 竪山真規, 西山亜由美, 城田松之, 舟山亮, 中山啓子, 三橋里美, 西野一三, 新堀哲也, 青木洋子

    多系統蛋白質症(MSP)の疾患概念確立および診断基準作成、診療体制構築に関する研究 平成30年度 総括・分担研究報告書(Web)　2019

  18. 一側上肢発症stiff-limb症候群の一例

    張替 宗介, 阪本 直広, 西山 亜由美, 菅野 直人, 菊池 昭夫, 黒田 宙, 青木 正志

    臨床神経学　59　(1)　57-57　2019/01

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

  19. 長期経過中に敗血症で死亡した家族性広汎型筋萎縮性側索硬化症の一剖検例

    宮代 麻由, 鬼塚 裕美, 武田 貴裕, 山本 智子, 鈴木 直輝, 西山 亜由美, 青木 正志, 北川 一夫, 柴田 亮行

    日本病理学会会誌　107　(1)　532-532　2018/04

    Publisher: (一社)日本病理学会

    ISSN： 0300-9181

  20. 多系統蛋白質症(MSP)関連hnRNPA1変異を伴い純粋封入体ミオパチーを呈した2家系の臨床・筋病理学的検討

    青木正志, 井泉瑠美子, 井泉瑠美子, 割田仁, 池田謙輔, 高橋俊明, 竪山真規, 鈴木直輝, 西山亜由美, 城田松之, 舟山亮, 中山啓子, 三橋里美, 西野一三, 新堀哲也, 青木洋子

    多系統蛋白質症(MSP)の疾患概念確立および診断基準作成、診療体制構築に関する研究 平成29年度 総括・分担研究報告書(Web)　2018

  21. 筋萎縮性側索硬化症モデル脊髄のアストロサイトにおける骨形成蛋白質の過剰発現

    四條友望, 割田仁, 鈴木直輝, 池田謙輔, 小野洋也, 秋山徹也, 光澤志緒, 西山亜由美, 井泉瑠美子, 青木正志

    日本再生医療学会総会(Web)　17th　2018

  22. 筋萎縮性側索硬化症ラットモデル脊髄における内在性再生機転

    割田仁, 四條友望, 池田謙輔, 小野洋也, 秋山徹也, 光澤志緒, 西山亜由美, 井泉瑠美子, 鈴木直輝, 青木正志

    再生医療　16　436　2017/02/01

    ISSN： 1347-7919

  23. 筋萎縮性側索硬化症モデルラットにおけるコンドロイチン硫酸プロテオグリカン受容体の異所性発現

    四條友望, 割田仁, 鈴木直輝, 池田謙輔, 秋山徹也, 小野洋也, 光澤志緒, 西山亜由美, 井泉瑠美子, 青木正志

    再生医療　16　435　2017/02/01

    ISSN： 1347-7919

  24. 筋ジストロフィー関連疾患の基盤的診断・治療開発研究 Dysferlinopathyおよび類似疾患の次世代シークエンサーを用いた診断および結合蛋白に注目した病態研究

    青木正志, 小野洋也, 井泉瑠美子, 鈴木直輝, 菅野新一郎, 高橋俊明, 割田仁, 加藤昌昭, 西山亜由美, 島倉奈緒子, 舟山亮, 中山啓子, 新堀哲也, 青木洋子, 三宅克也, 三宅克也

    筋ジストロフィー関連疾患の基盤的診断・治療開発研究 平成26-28年度 総括研究報告書　18‐20　2017

  25. 多系統プロテイノパチー連鎖性hnRNPA1変異に起因する孤立性封入体ミオパチー(Isolated inclusion body myopathy caused by a multisystem proteinopathy-linked hnRNPA1 mutation)

    井泉 瑠美子, 割田 仁, 新堀 哲也, 高橋 俊明, 竪山 真規, 鈴木 直輝, 西山 亜由美, 城田 松之, 舟山 亮, 中山 啓子, 三橋 里美, 西野 一三, 青木 洋子, 青木 正志

    臨床神経学　56　(Suppl.)　S280-S280　2016/12

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  26. ヌーナン症候群と類縁疾患の遺伝子診断体制の確立とその病態解明

    青木洋子, 梅木郁美, 大場大樹, 西山亜由美, 高原真吾, 矢尾板全子, 井上晋一, 松原洋一, 新堀哲也

    日本遺伝子診療学会大会プログラム・抄録集　23rd　77　2016/10/06

  27. 神経変性疾患領域における基盤的調査研究 家族性ALSにおける遺伝子解析

    青木正志, 鈴木直輝, 加藤昌昭, 割田仁, 井泉瑠美子, 西山亜由美, 秋山徹也, 島倉奈緒子

    神経変性疾患領域における基盤的調査研究 平成27年度 総括・分担研究報告書　66‐67　2016

  28. 日本のFUS/TLS遺伝子関連家族性ALS症例における遺伝子型-表現型相関(Genotype-phenotype correlation with FUS/TLS-linked familial ALS cases in Japan)

    秋山 徹也, 鈴木 直輝, 割田 仁, 加藤 昌昭, 西山 亜由美, 井泉 瑠美子, 池田 謙輔, 小野 洋也, 四條 友望, 青木 正志

    臨床神経学　55　(Suppl.)　S237-S237　2015/12

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  29. 小児科・産科領域疾患の大規模遺伝子解析ネットワークとエピゲノム解析拠点整備に関する研究 次世代シークエンサーを駆使した先天性疾患の遺伝子解析と病態解明

    青木洋子, 新堀哲也, 井上晋一, 井泉瑠美子, 守谷充司, 大場大樹, 矢尾板全子, 西山亜由美

    小児科・産科領域疾患の大規模遺伝子解析ネットワークとエピゲノム解析拠点整備に関する研究 平成26年度 委託業務成果報告書　2015

  30. 細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 次世代シークエンサーを用いたRAS/MAPK症候群の遺伝子解析

    新堀哲也, 井泉瑠美子, 守谷充司, 大場大樹, 矢尾板全子, 西山亜由美

    細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 平成26年度 委託業務成果報告書　2015

  31. 細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 医療機関・患者への情報提供とプロジェクト推進班会議の開催

    青木洋子, 松原洋一, 緒方勤, 黒澤健司, 岡本伸彦, 水野誠司, 大橋博文, 川目裕, 呉繁夫, 梅澤明弘, 新堀哲也, 横谷進, 深見真紀, 井上晋一, 井泉瑠美子, 守谷充司, 矢尾板全子, 大場大樹, 西山亜由美, 吉井啓示, 三島祐子, 清水健司, 小林朋子

    細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 平成26年度 委託業務成果報告書　2015

  32. 細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 シグナル伝達異常症の遺伝子解析とモデルマウスにおける治療法開発

    青木洋子, 新堀哲也, 井上晋一, 井泉瑠美子, 守谷充司, 矢尾板全子, 大場大樹, 西山亜由美, 富田幸子, 中嶌八隅

    細胞内シグナル伝達異常による先天奇形症候群の病態解明と治療法開発の研究 平成26年度 委託業務成果報告書　2015

  33. 神経変性疾患領域における基盤的調査研究 家族性ALSにおける遺伝子解析

    青木正志, 加藤昌昭, 割田仁, 鈴木直輝, 井泉瑠美子, 西山亜由美, 島倉奈緒子, 安藤里紗

    神経変性疾患領域における基盤的調査研究 平成26年度 総括・分担研究報告書　54‐56　2015

  34. 筋萎縮性側索硬化症モデル成体脊髄における潜在的neurogenic niche

    割田 仁, 水野 秀紀, 加藤 昌昭, 井泉 瑠美子, 西山 亜由美, 鈴木 直輝, 船越 洋, 糸山 泰人, 青木 正志

    臨床神経学　54　(Suppl.)　S37-S37　2014/12

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

  35. FUS/TLS遺伝子変異型とALS表現形の関連について

    加藤 昌昭, 割田 仁, 井泉 瑠美子, 西山 亜由美, 青木 正志

    臨床神経学　54　(Suppl.)　S149-S149　2014/12

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

    eISSN： 1882-0654

  36. 当分野におけるヌーナン症候群及び類縁疾患の遺伝子解析の現状

    新堀 哲也, 矢尾板 全子, 守谷 充司, 井泉 瑠美子, 大場 大樹, 西山 亜由美, 井上 晋一, 呉 繁夫, 松原 洋一, 青木 洋子

    日本小児科学会雑誌　118　(5)　876-877　2014/05

    Publisher: (公社)日本小児科学会

    ISSN： 0001-6543

  37. 神経変性疾患に関する調査研究 日本人家族性ALSにおけるFUS/TLS遺伝子変異の重要性について

    青木正志, 加藤昌昭, 割田仁, 井泉瑠美子, 西山亜由美, 島倉奈緒子, 安藤里紗

    神経変性疾患に関する調査研究 平成25年度 総括・分担研究報告書　2014

  38. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 先天奇形症候群の原因遺伝子解析とその病態の解明

    青木洋子, 新堀哲也, 井上晋一, 井泉瑠美子, 守谷充司, 大場大樹, 西山亜由美, 松原洋一

    次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 平成25年度 総括・分担研究報告書　2014

  39. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 次世代シークエンサーを用いた遺伝性疾患新規原因遺伝子探索

    新堀哲也, 井泉瑠美子, 矢尾板全子, 西山亜由美

    次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 平成23-25年度 総合研究報告書　2014

  40. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 次世代シークエンサーを用いた遺伝性疾患新規原因遺伝子探索

    新堀哲也, 井泉瑠美子, 矢尾板全子, 西山亜由美

    次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 平成25年度 総括・分担研究報告書　2014

  41. 免疫グロブリン大量療法が奏効した両側腕神経叢炎の1例

    西山 亜由美, 菅野 直人, 割田 仁, 竪山 真規, 青木 正志

    末梢神経　24　(2)　414-414　2013/12

    Publisher: 日本末梢神経学会

    ISSN： 0917-6772

  42. 球脊髄性筋萎縮症における下肢振戦の検討

    西山 亜由美, 菅野 直人, 加藤 昌昭, 竪山 真規, 青木 正志

    臨床神経学　53　(12)　1440-1440　2013/12

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

  43. 脊髄長大病変に髄液多形核白血球増多を伴う疾患群について

    黒田 宙, 高橋 利幸, 佐藤 ダグラス, 西山 亜由美, 三浦 永美子, 西山 修平, 三須 建郎, 中島 一郎, 藤原 一男, 青木 正志

    神経免疫学　18　(1)　113-113　2013/11

    Publisher: 日本神経免疫学会

    ISSN： 0918-936X

  44. A case series of longitudinally-extended spinal cord lesion with increased polymorphonuclear leukocytes in CSF

    H. Kuroda, T. Takahashi, D. Sato, A. Nishiyama, E. Miura, S. Nishiyama, N. Sugeno, T. Misu, I. Nakashima, K. Fujihara, M. Aoki

    MULTIPLE SCLEROSIS JOURNAL　19　(11)　316-317　2013/10

    ISSN： 1352-4585

    eISSN： 1477-0970

  45. 潜在発作のビデオ脳波記録が認知症との鑑別に有用であった高齢発症側頭葉てんかんの一例

    西山 亜由美, 神 一敬, 加藤 量広, 板橋 尚, 飯塚 統, 岩崎 真樹, 青木 正志, 中里 信和

    臨床神経学　53　(9)　757-757　2013/09

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

  46. NMO急性期治療としてリツキシマブが有効であった1例

    西山 修平, 西山 亜由美, 三須 建郎, 中島 一郎, 藤原 一男, 青木 正志

    神経治療学　30　(5)　695-695　2013/09

    Publisher: 日本神経治療学会

    ISSN： 0916-8443

    eISSN： 2189-7824

  47. 治療に難渋した傍脊柱肩甲型筋炎の1例

    大嶋 龍司, 菅野 直人, 竪山 真規, 鈴木 千尋, 坪井 博文, 西山 亜由美, 青木 正志

    臨床神経学　53　(3)　262-262　2013/03

    Publisher: (一社)日本神経学会

    ISSN： 0009-918X

  48. 全エクソンシークエンスによるdysferlin遺伝子変異のスクリーニング法の検討

    高橋俊明, 加藤昌昭, 西山亜由美, 井泉瑠美子, 鈴木直輝, 竪山真規, 八木沼智香子, 島倉奈緒子, 田中洋康, 吉岡勝, 今野秀彦, 糸山泰人, 青木正志

    日本人類遺伝学会大会プログラム・抄録集　58th　189　2013

  49. [Radial nerve palsy as a presenting feature of neuralgic amyotrophy].

    Hirofumi Tsuboi, Naoto Sugeno, Ayumi Nishiyama, Maki Tateyama, Masashi Aoki

    Rinsho shinkeigaku = Clinical neurology　53　(4)　312-5　2013

    Publisher: (一社)日本神経学会

    DOI： 10.5692/clinicalneurol.53.312 　

    ISSN： 0009-918X

    eISSN： 1882-0654

  50. 橈骨神経麻痺が前景に立ち、4枝の神経障害が主体であったNeuralgic amyotrophyの一例

    坪井 博文, 菅野 直人, 西山 亜由美, 竪山 真規, 青木 正志

    末梢神経　23　(2)　406-406　2012/12

    Publisher: 日本末梢神経学会

    ISSN： 0917-6772

  51. NMO急性期治療としてリツキシマブが有効であった1例

    西山 亜由美, 西山 修平, 三須 建郎, 中島 一郎, 青木 正志, 藤原 一男

    日本神経免疫学会学術集会抄録集　24回　108-108　2012/09

    Publisher: 日本神経免疫学会

Show all ︎Show first 5

Research Projects 3

  1. 家族性ALSにおけるゲノム配列・リピート長に着目した網羅的解析と病態解明

    西山 亜由美

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2026/04/01 - 2029/03/31

  2. 家族性ALSで見出した新規遺伝子変異の病原性解明パイプラインの確立

    西山 亜由美

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究

    Category: 若手研究

    Institution: 東北大学

    2019/04/01 - 2023/03/31

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    1991年より研究代表者らの施設で、全国より集積した日本人家族性ALS家系に新たに7家系を加えた134家系を対象とし、その臨床像を確認し、次世代シークエンサーを用いて網羅的遺伝子解析を行った。 新規家系では運動ニューロン病関連63遺伝子に関するターゲットリシークエンス解析を行った。病原遺伝子変異未同定例に対してエクソーム解析を実施した。 25のSOD1遺伝子変異を41家系（31%）に同定した。SOD1変異例は孤発例に比べ、やや若年、下肢発症、長期経過例が多くみられた。変異によって地域的集積を認めた。12家系（9%）にみられたFUS変異は若年発症、上肢近位筋もしくは頸部発症で進行が速いという特徴があった。さらに3家系（2%）にTARDBP変異を同定し、一部は病理学的検知を得た。加えて1家系にOPTNのp.E478G変異を同定した。 沖縄出身の1家系においては、近位筋優位運動感覚ニューロパチーの病的変異であるTFG変異を同定した。また、遺伝性痙性対麻痺に関連するALDH18A1遺伝子変異を見出した。 総じて、45％に病原遺伝子変異を同定し、1家系には新規のVCP遺伝子変異を見出した。さらに、バイオインフォマティクスによりALS関連遺伝子において複数の新たな候補遺伝子変異を検出した。引き続き、培養細胞株に各候補遺伝子変異を導入した形質の解析、健常ヒトiPS細胞由来運動ニューロンに目的変異を導入した細胞種選択的な病態解明に取り組み、新規遺伝子変異の病原性解明パイプラインの確立を目指す。

  3. Elucidation of the pathogenicity of novel gene mutations detected through comprehensive genetic analysis in familial ALS

    Nishiyama Ayumi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2017/08/25 - 2019/03/31

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    The purpose of this research is to reveal the pathogenicity of gene mutations detected in familial amyotrophic lateral sclerosis (ALS) and the underlying mechanism of selective motor neuron degeneration. We performed comprehensive genetic analysis using next-generation sequencer in a consecutive series of 134 Japanese familial ALS pedigrees. We identified known mutations in approximately half of all cases. In the remaining genetically unidentified cases, we have found novel candidate mutations and perform validation of their significance.