BRAIN and NERVE－神経研究の進歩75巻2号

2023年02月発行

特集 多系統萎縮症の新診断基準とこれからの診療

New MDS criteria時代の新しい治療

著者： 長谷川隆文¹

所属機関： ¹東北大学大学院医学系研究科神経・感覚器病態学講座神経内科学分野

ページ範囲：P.149 - P.156

文献概要

多系統萎縮症（multiple system atrophy：MSA）の病態理解が進む中，疾患修飾療法開発に努力が注がれている。これまでにαシヌクレイン蛋白の凝集抑制，神経炎症，栄養因子低下を是正する複数の疾患修飾薬開発が試みられてきたが，ほとんどは失敗に終わっている。この度MSA診断基準が改訂され，より早期に信頼性の高い診断が可能となるとともに，新たに前駆期MSAの基準が制定され，トランスレーショナルギャップの縮小が期待されている。

参考文献

1）Yoshida S, Hasegawa T: Deciphering the prion-like behavior of pathogenic protein aggregates in neurodegenerative diseases. Neurochem Int 155: 105307, 2022［doi: 10.1016/j.neuint.2022.105307］

2）Schweighauser M, Shi Y, Tarutani A, Kametani F, Murzin AG, et al: Structures of α-synuclein filaments from multiple system atrophy. Nature 585: 464-469, 2020

3）Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, et al: The movement disorder society criteria for the diagnosis of multiple system atrophy. Mov Disord 37: 1131-1148, 2022

4）Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H: Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249: 180-182, 1998

5）Hasegawa T: Pathogenesis of multiple system atrophy. Neurol Clin Neurosci 1: 189-194, 2013

6）Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, et al: Suppression of dynamin GTPase decreases α-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. Mol Neurodegener 7: 38, 2012［doi: 10.1186/1750-1326-7-38］

7）Wenning GK, Stefanova N, Jellinger KA, Poewe W, Schlossmacher MG: Multiple system atrophy: a primary oligodendrogliopathy. Ann Neurol 64: 239-246, 2008

8）Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, et al: Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A 112: E5308-5317, 2015［doi: 10.1073/pnas.1514475112］

9）Jellinger KA, Lantos PL: Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. Acta Neuropathol 119: 657-667, 2010

10）Marmion DJ, Peelaerts W, Kordower JH: A historical review of multiple system atrophy with a critical appraisal of cellular and animal models. J Neural Transm (Vienna) 128: 1507-1527, 2021

11）Mitsui J, Matsukawa T, Ishiura H, Fukuda Y, Ichikawa Y, et al: Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 369: 233-244, 2013

12）Watanabe H, Saito Y, Terao S, Ando T, Kachi T, et al: Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 125: 1070-1083, 2002

13）Low PA, Robertson D, Gilman S, Kaufmann H, Singer W, et al: Efficacy and safety of rifampicin for multiple system atrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 13: 268-275, 2014

14）Levin J, Maaß S, Schuberth M, Respondek G, Paul F, et al: The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach. J Neural Transm (Vienna) 123: 439-445, 2016

15）Saccà F, Marsili A, Quarantelli M, Brescia Morra V, Brunetti A, et al: A randomized clinical trial of lithium in multiple system atrophy. J Neurol 260: 458-461, 2013

16）Palma JA, Martinez J, Millar Vernetti P, Ma T, Perez MA, et al: mTOR inhibition with sirolimus in multiple system atrophy: a randomized, double-blind, placebo-controlled futility trial and 1-year biomarker longitudinal analysis. Mov Disord 37: 778-789, 2022

17）Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, et al: Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord 25: 97-107, 2010

18）Poewe W, Seppi K, Fitzer-Attas CJ, Wenning GK, Gilman S, et al: Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial. Lancet Neurol 14: 145-152, 2015

19）Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, et al: Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS Study. Brain 132: 156-171, 2009

20）Stefanova N: Translational therapies for multiple system atrophy: bottlenecks and future directions. Auton Neurosci 211: 7-14, 2018

21）Fjord-Larsen L, Thougaard A, Wegener KM, Christiansen J, Larsen F, et al: Nonclinical safety evaluation, pharmacokinetics, and target engagement of Lu AF82422, a monoclonal IgG1 antibody against alpha-synuclein in development for treatment of synucleinopathies. MAbs 13: 1994690, 2021［doi: 10.1080/19420862.2021.1994690］

22）Meissner WG, Traon AP, Foubert-Samier A, Galabova G, Galitzky M, et al: A phase 1 randomized trial of specific active α-synuclein immunotherapies PD01A and PD03A in multiple system atrophy. Mov Disord 35: 1957-1965, 2020

23）Conway KS, Camelo-Piragua S, Fisher-Hubbard A, Perry WR, Shakkottai VG, et al: Multiple system atrophy pathology is associated with primary Sjögren's syndrome. JCI Insight 5: e138619, 2020［doi: 10.1172/jci.insight.138619］

24）Levin J, Nübling G, Giese A, Janzen A, Oertel W: Neuroprotective treatment of idiopathic, genetic and atypical Parkinson's disease with alpha-synuclein-Pathology. Nervenarzt 92: 1249-1259, 2021

25）Lee PH, Lee JE, Kim HS, Song SK, Lee HS, et al: A randomized trial of mesenchymal stem cells in multiple system atrophy. Ann Neurol 72: 32-40, 2012

26）Novak P, Pimentel Maldonado DA, Novak V: Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: a double-blinded placebo-controlled pilot study. PLOS ONE 14: e0214364, 2019［doi: 10.1371/journal.pone.0214364］

27）Bassil F, Canron MH, Vital A, Bezard E, Li Y, et al: Insulin resistance and exendin-4 treatment for multiple system atrophy. Brain 140: 1420-1436, 2017

28）Jung Lee J, Han Yoon J, Jin Kim S, Soo Yoo H, Jong Chung S, et al: Inosine 5'-monophosphate to raise serum uric acid level in multiple system atrophy (IMPROVE-MSA study). Clin Pharmacol Ther 109: 1274-1281, 2021

29）Quintino L, Avallone M, Brännstrom E, Kavanagh P, Lockowandt M, et al: GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration. Gene Ther 26: 57-64, 2019

30）Mitsui J, Koguchi K, Momose T, Takahashi M, Matsukawa T, et al: Three-year follow-up of high-dose ubiquinol supplementation in a case of familial multiple system atrophy with compound heterozygous COQ2 mutations. Cerebellum 16: 664-672, 2017