ログイン
ランキング
お知らせ
ログイン
文献詳細
特集 神経難病をクスリで治す—薬物開発の現況と近未来への展望
文献概要
アルツハイマー病（AD）の臨床試験では，抗アミロイド療法薬や抗タウ療法薬を中心に多くの疾患修飾薬の治験が進められてきたが，ほとんどは失敗に終わっている。今後，効率的な臨床試験によって新薬の開発を成功させるためには，より早期の対象の登録，新しいバイオマーカーや評価基準，無益性解析やベイジアン・アダプティブ・デザインなどの革新的な試験デザインが必須である。
参考文献
1)Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM: Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 3: 186-191, 2007
2)Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, et al: Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31: 1275-1283, 2010
3)Jack CR Jr., Knopman DS, Weigand SD, Wiste HJ, Vemuri P, et al: An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol 71: 765-775, 2012
4)Kozauer N, Katz R: Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med 368: 1169-1171, 2013
5)Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K: Alzheimer's disease drug development pipeline: 2019. Alzheimers Dement 5: 272-293, 2019
6)Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, et al: Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388: 2873-2884, 2016
7)Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, et al: Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173-177, 1999
8)Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, et al; Alzheimer's Disease Cooperative Study Steering Committee; Solanezumab study group: Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med 370: 311-321, 2014
9)Honig LS, Vellas B, Woodward M, Boada M, Bullock R, et al: Trial of Solanezumab for mild dementia due to Alzheimer's disease. N Engl J Med 378: 321-330, 2018
10)Cummings JL, Cohen S, van Dyck CH, Brody M, Curtis C, et al: ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Neurology 90: e1889-e1897, 2018
11)Cummings J, Cho W, Ward M, Friesenhahn M, Brunstein F, et al: A randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and safety of crenezumab in patients with mild to moderate Alzheimer's disease. Alzheimers Demen 10: 275, 2014
12)Melville NA: Crenezumab Fails in Alzheimer's but Is There a Silver Lining? http://www.medscape.com/viewarticle/828883（最終閲覧日2019年10月11日）
13)Alzforum: Aducanumab. http://www.alzforum.org/therapeutics/aducanumab（最終閲覧日2019年10月11日）
14)Bohrmann B, Baumann K, Benz J, Gerber F, Huber W, et al: Gantenerumab: a novel human anti-beta-amyloid antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis 28: 49-69, 2012
15)Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, et al: Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61: 46-54, 2003
16)Ryan JM, Grundman M: Anti-amyloid-beta immunotherapy in Alzheimer's disease: ACC-001 clinical trials are ongoing. J Alzheimers Dis 17: 243, 2009
17)Muhs A, Hickman DT, Pihlgren M, Chuard N, Giriens V, et al: Liposomal vaccines with conformation-specific amyloid antigens define immune response and efficacy in APP transgenic mice. Proc Natl Acad Sci U S A 104: 9810-9815, 2007
18)Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, et al: Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomized, double-blind, placebo-controlled, first-in-human study. Lancet Neurol 11: 597-604, 2012
19)Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, et al: Long-term treatment with active Aβ immunotherapy with CAD106 in mild Alzheimer's disease. Alzheimers Res Ther 7: 23, 2015［doi: 10.1186/s13195-015-0108-3］
20)Lopez Lopez C, Tariot PN, Caputo A, Langbaum JB, Liu F, et al: The Alzheimer's prevention initiative generation program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer's disease. Alzheimers Dement 5: 216-227, 2019
21)Hu X, Hicks CW, He W, Wong P, Macklin WB, et al: Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 9: 1520-1525, 2006
22)Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, et al: Control of peripheral nerve myelination by the beta-secretase BACE1. Science 314: 664-666, 2006
23)Forman M, Tseng J, Palcza J, Leempoels J, Ramael S, et al: The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid peptides in healthy subjects: results from a rising single dose study (PL02. 004). Neurology 78: PL02.004, 2012
24)Forman MS, Palcza J, Tseng J, Leempoels J, Ramael S, et al: The novel BACE inhibitor MK-8931 dramatically lowers CSF Abeta peptide in patients with mild to moderate Alzheimer's disease. The 11th International Conference on Alzheimer's and Parkinson's Disease, Florence, Italy, 2013
25)Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, et al: Randomized trial of Verubecestat for mild-to-moderate Alzheimer's disease. N Engl J Med 378: 1691-1703, 2018
26)Egan MF, Kost J, Voss T, Mukai Y, Aisen PS, et al: Randomized trial of Verubecestat for prodromal Alzheimer's disease. N Engl J Med 380: 1408-1420, 2019
27)Alzforum: AZD3293 (Lanabecestat) http://www.alzforum.org/therapeutics/azd3293-0（最終閲覧日2019年10月11日）
28)Xiao S, Zhang Z, Geng M, GV-971 Study Group. Phase 3 clinical trial of a novel and multi-targeted oligosaccharide in patients with mild-moderate AD in China. Clinical Trials on Alzheimer's Disease. Barcelona, Spain, October 25, 2018
29)Rosen WG, Mohs RC, Davis KL: A new rating scale for Alzheimer's disease. Am J Psychiatry 141: 1356-1364, 1984
30)Boothby H, Mann AH, Barker A: Factors determining interrater agreement with rating global change in dementia: the cibic-plus. Int J Geriatr Psychiatry 10: 1037-1045, 1995
31)Braak H, Braak E: Evolution of the neuropathology of Alzheimer's disease. Acta Neurol Scand Suppl 165: 3-12, 1996
32)Cummings J, Lee G, Ritter A, Zhong K: Alzheimer`s disease drug development pipeline: 2018. Alzheimers Dement 4: 195-214, 2018
33)Bakota L, Brandt R: Tau biology and tau-directed therapies for Alzheimer's disease. Drugs 76: 301-313, 2016
34)Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, et al: Efficacy and safety of tau-aggregation inghibitor therapy in patients with mild or mpderate Alzheimer's disease: a randomized, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388: 2873-2884, 2016
35)Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM: Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 27: 9115-9129, 2007
36)Hampel H, Lista S, Teipel SJ, Garaci F, Nistico R, et al: Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: a long-range point of view beyond 2020. Biochem Pharmacol 88: 426-449, 2014
37)McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, et al: The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 263-269, 2011
38)Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, et al: The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 270-279, 2011
39)Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, et al: Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol 13: 614-629, 2014
40)Doody RS, Farlow M, Aisen PS; Alzheimer's Disease Cooperative Study Data Analysis and Publication Comittee: Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. N Engl J Med 370: 1460, 2014
41)Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, et al: NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement 14: 535-562, 2018
42)Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, et al: High performance plasma amyloid-β biomarkers for Alzheimer's disease. Nature 554: 249-254, 2018
43)Ashton NJ, Leuzy A, Lim YM, Troakes C, Hortobagyi T, et al: Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration. Acta Neuropathol Commun 7: 5, 2019［doi: 10.1186/s40478-018-0649-3］
44)Wang J, Logovinsky V, Hendrix SB, Stanworth SH, Perdomo C, et al: ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials. J Neurol Neurosurg Psychiatry 87: 993-999, 2016
45)Folstein MF, Folstein SE, McHugh PR: “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198, 1975
46)Appleby BS, Nacopoulos D, Milano N, Zhong K, Cummings JL: A review: treatment of Alzheimer's disease discovered in repurposed agents. Dement Geriatr Cogn Disord 35: 1-22, 2013
47)Appleby BS, Cummings JL: Discovering new treatments for Alzheimer's disease by repurposing approved medications. Curr Top Med Chem 13: 2306-2327, 2013
48)Barnes DE, Yaffe K: The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 10: 819-828, 2011
掲載誌情報
