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Title 筋委縮性側索硬化症
Subtitle 特集 神経難病の今 〜疫学・成因・治療の研究最前線〜
Authors 大久保卓哉
Authors (kana)
Organization 横浜市立みなと赤十字病院脳神経内科, 横浜市認知症疾患医療センター(中区・西区), 東京医科歯科大学医学部
Journal Pharma Medica
Volume 39
Number 3
Page 15-22
Year/Month 2021 / 3
Article 報告
Publisher メディカルレビュー社
Abstract 「はじめに」 筋萎縮性側索硬化症(amyotrophic lateral sclerosis: ALS)は, 上位運動ニューロンと下位運動ニューロンが特異的に変性し, 球麻痺, 四肢筋力低下, 筋萎縮が進行する, いまだに根本的な治療のない神経難病の1つである. 近年では, 遺伝学的, 分子生物学的, 神経病理学的研究の成果により, 診断技術の進歩, 根本的治療の糸口が見出されようとしている. 本稿では, 疫学, 成因, 治療のそれぞれについて, 最新の話題を概説したい. 「I. 疫学」 日本におけるALSの発症率は, 2009年4月から2010年3月の厚生労働省特定疾患登録患者データからは2.2(2.1〜2.3: 95%信頼区間, 以下同様)/10万人/年で, 男女発症率比は約1.5で男性に多いとされている. また, 2013年に発刊された『筋萎縮性側索硬化症診療ガイドライン』(日本神経学会編)では, ALSの発症率は1.1〜2.5/10万人/年, 有病率は7.0〜8.5/10万人/年と記載されている.
Practice 薬学
Keywords ALSの疫学, ALSの成因, ALSのバイオマーカー, ALSの治療
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参考文献

  • 1) Doi Y, Atsuta N, Sobue G, et al. Prevalence and incidence of amyotrophic lateral sclerosis in Japan. J Epidemiol. 2014;24:494-9.
    pubmed
  • 2) 日本神経学会, 「筋萎縮性側索硬化症診療ガイドライン」作成委員会(編). 筋萎縮性側索硬化症診療ガイドライン2013. 東京:南江堂;2013.p.1-21.
  • 3) Shahrizalia N, Sobue G, Kuwahara S, et al. Amyotrophic lateral sclerosis and motor neuron syndromes in Asia. J Neurol Neurosurg Psychiatry. 2016;87:821-30.
  • 4) Xu L, Liu T, Liu L, et al. Global variation in prevalence and incidence of ALS: a systematic review and meta-analysis. J Neurol. 2020;267:944-53.
  • 5) GBD 2016 Motor Neuron Disease Collaborators. Global, regional, and national burden of motor neuron diseases 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17:1083-97.
    pubmed
残りの55件を表示する
  • 6) Renton AE, Chio A, Traynor B. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17:17-23.
    pubmed
  • 7) Nakamura R, Sone J, Atsuta N, et al. Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort. Neurobiol Aging. 2016;39:219.e1-8.
  • 8) Nishiyama A, Niihori T, Warita H, et al. Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis. Neurobiol Aging. 2017;53:194.e1-8.
  • 9) Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59-62.
    pubmed
  • 10) Arai T, Hasegawa M, Akiyama H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351:602-11.
    pubmed
  • 11) Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130-3.
  • 12) Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72:257-68.
  • 13) DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72:245-56.
    pubmed
  • 14) Ilieva H, Polymenidou M, Cleveland DW. Non-cell autonomous toxicity in neurodegenerative disorders-ALS and beyond. J Cell Biol. 2009;187:761-72.
    pubmed
  • 15) Hayashi Y, Homma K, Ichijo H. SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS. Adv Biol Regul. 2016;60:95-104.
    pubmed
  • 16) Ido A, Fukuyama H, Urushitani M. Protein misdirection inside and outside motor neurons in Amyotrophic Lateral Sclerosis(ALS): a possible clue for therapeutic strategies. Int J Mol Sci. 2011;12:6980-7003.
  • 17) Prudencio M, Durazo A, Whitelegge JP, et al. An examination of wild-type SOD1 in modulating the toxicity and aggregation of ALS-associated mutant SOD1. Hum Mol Genet. 2010;19:4774-89.
  • 18) Chia R, Tattum MH, Jones S, et al. Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis. PLoS One. 2010;5:e10627.
    pubmed
  • 19) Grad LI, Guest WC, Yanai A, et al. Intermolecular transmission of superoxide dismutase 1 misfolding in living cells. Proc Natl Acad Sci USA. 2011;108:116398-403.
  • 20) Munch C, O'Brien J, Bertolotti A. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proc Natl Acad Sci USA. 2011;108:3548-53.
    pubmed
  • 21) Furukawa Y, Kaneko K, Watanabe S, et al. A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element(TAR)DNA-binding protein-43 inclusions. J Biol Chem. 2011;286:18664-72.
  • 22) Urushitani M, Sik A, Sakurai T, et al. Chromogranin-mediated secretion of mutant superoxidase dismutase proteins linked to amyotrophic lateral sclerosis. Nat Neurosci. 2006;9:108-18.
  • 23) Bosco DA, Morfini G, Karabacak NM, et al. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci. 2010;13:1396-403.
  • 24) Pesiridis GS, Tripathy K, Tanik S, et al. A "two-hit" hypothesis for inclusion formation by carboxyl-terminal fragments of TDP-43 protein linked to RNA depletion and impaired microtubule-dependent transport. J Biol Chem. 2011;286:18845-55.
  • 25) Gasset-Rosa F, Lu S, Yu H, et al. Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death. Neuron. 2019;102:339-57.e7.
  • 26) Swarup V, Phaneuf D, Dupre N, et al. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB-mediated pathogenic pathways. J Exp Med. 2011;208:2429-47.
  • 27) Winton MJ, Igaz LM, Wong MM, et al. Disturbance of nuclear and cytoplasmic TAR DNA-binding protein(TDP-43)induces disease-like redistribution, sequestration, and aggregate formation. J Biol Chem. 2008;283:13302-9.
    pubmed
  • 28) Prasad A, Bharathi V, Sivalingam V, et al. Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis. Front Mol Neurosci. 2019;12:25.
    pubmed
  • 29) Bentmann E, Neumann M, Tahirovic S, et al. Requirements for stress granule recruitment of fused in sarcoma(FUS)and TAR DNA-binding protein of 43 kDa(TDP-43). J Biol Chem. 2012;287:23079-94.
    pubmed
  • 30) Shiina N. Liquid-and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules. J Biol Chem. 2019;294:3532-8.
    pubmed
  • 31) Watanabe S, Inami H, Oiwa K, et al. Aggresome formation and liquid-liquid phase separation independently induce cytoplasmic aggregation of TDP-43. Cell Death Dis. 2020;11:909.
    pubmed
  • 32) Taylor JP, Brown RH, Cleveland DW. Decoding ALS:from genes to mechanism. Nature. 2016;539:197-206.
    pubmed
  • 33) Sproviero W, Shatunov A, Stahl D, et al. ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiol Aging. 2017;51:178.e1-9.
  • 34) Becker LA, Huang B, Bieri G, et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017;544:367-71.
    pubmed
  • 35) Klim JR, Vance C, Scotter EL. Antisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis:Existing and emerging targets. Int J Biochem Cell Biol. 2019;110:149-53.
    pubmed
  • 36) 富山弘幸. わが国のALSにおけるC9ORF72. 臨床神経. 2013;53:1074-76.
  • 37) Balendra R, Isaacs AM. C9orf72-mediatd ALS and FTD:multiple pathways to disease. Nat Rev Neurol. 2018;14:544-58.
  • 38) Saberi S, Stauffer JE, Jiang J, et al. Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis. Acta Neuropathol. 2018;135:459-74.
    pubmed
  • 39) Aladesuyi Arogundade O, Stauffer JE, Saberi S, et al. Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study. Acta Neuropathol. 2019;137:527-30.
    pubmed
  • 40) Jiang J, Zhu Q, Gendron TF, et al. Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs. Neuron. 2016;90:535-50.
    pubmed
  • 41) O'Rourke JG, Bogdanik L, Yanez A, et al. C9orf72 is required for proper macrophage and microglial function in mice. Science. 2016;351:1324-9.
    pubmed
  • 42) Vu LT, Bowser R. Fluid-based biomarkers for Amyotrophic lateral sclerosis. Neurotherapeutics. 2017;14:119-34.
    pubmed
  • 43) 大久保卓哉. III. 検査, 機能評価 4. 診断や進行の目安となるバイオマーカーはありますか?(画像, 血液・脳脊髄液など)鈴木則宏(監), 青木正志(編), 運動ニューロン疾患(神経内科Clinical Questions & Pearls). 東京:中外医学社;2017.p.130-40.
  • 44) Zucchi E, Bonetto V, Soraru G, et al. Neurofilaments in motor neuron disorders:towards promising diagnostic and prognostic biomarkers. Mol Neurodegener. 2020;15:58.
    pubmed
  • 45) Ganesalingam J, An J, Shaw CE, et al. Combination of neurofilament heavy chain and compleent C3 as CSF biomarkers for ALS. J Neurochem. 2011;117:528-37.
    pubmed
  • 46) Shepheard SR, Chataway T, Schultz DW, et al. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis. PLoS One. 2014;9:e87398.
    pubmed
  • 47) Shepheard SR, Wuu J, Cardoso M, et al. Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Neurology. 2017;88:1137-43.
    pubmed
  • 48) Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994;330:585-91.
  • 49) Lacomblez L, Bensimon G, Leigh PN, et al. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group II. Lancet. 1996;347:1425-31.
  • 50) Miller RG, Jackson CE, Kasarskis EJ, et al. Practice Parameter update:The care of the patient with amyotrophic lateral sclerosis:Multidisciplinary care, symptom management, and cognitive/behavioral impairment(an evidence-based review), Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1227-33.
  • 51) 柳澤信夫, 田代邦雄, 東儀英夫, 他. 日本における筋萎縮性側索硬化症患者に対するRiluzoleの二重盲検比較試験. 医学のあゆみ. 1997;182:851-66.
    Medical*Online
  • 52) Bensimon G, Lacomblez L, Delumeau JC, et al. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J Neurol. 2012;249:609-15.
    pubmed
  • 53) Thakor K, Naud S, Howard D, et al. Effect of riluzole on weight in short-term and long-term survivors of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2021;1-8.Online ahead of print.
  • 54) Urushitani M, Kurisu J, Tsukita K, et al. Proteasomal inhibition by misfolded mutant superoxide dismutase 1 induces selective motor neuron death in familial amyotrophic lateral sclerosis. J Neurochem. 2002;83:1030-42.
    pubmed
  • 55) D'Amico E, Factor-Litvak P, Santella RM, et al. Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis. Free Radic Biol Med. 2013;65:509-27.
    pubmed
  • 56) Ikawa M, Okazawa H, Tsujikawa T, et al. Increased oxidative stress is related to disease severity in the ALS motor cortex: A PET study. Neurology. 2015;8:2033-9.
  • 57) Writing Group;Edaravone(MCI-186)ALS 19 Study Group. Safety and efficacy of edaravone in well-defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16:505-12.
  • 58) Okada M, Yamashita S, Ueyama H, et al. Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis. eNeurologicalSci. 2018;11:11-4.
    pubmed
  • 59) Shefner J, Heima-Patterson T, Pioro EP, et al. Long-term edaravone efficacy in amyotrophic lateral sclerosis:Post-hoc analyses of Study 19(MCI186-19). Muscle Nerve. 2020;61:218-21.
  • 60) Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1-2 trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020;383:109-19.
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