OPINION FTD and ALS-translating mouse studies into clinical trials

被引:61
作者
Ittner, Lars M. [1 ]
Halliday, Glenda M. [2 ,3 ]
Kril, Jillian J. [4 ,5 ]
Goetz, Juergen [6 ]
Hodges, John R. [2 ,3 ]
Kiernan, Matthew C. [7 ]
机构
[1] Univ New S Wales, Dementia Res Unit, Sch Med Sci, Sydney, NSW 2052, Australia
[2] Univ New S Wales, Sydney, NSW 2031, Australia
[3] Neurosci Res Australia, Sydney, NSW 2031, Australia
[4] Univ Sydney, Sydney Med Sch, Discipline Med, Sydney, NSW 2006, Australia
[5] Univ Sydney, Sydney Med Sch, Discipline Pathol, Sydney, NSW 2006, Australia
[6] Univ Queensland, Queensland Brain Inst, Clem Jones Ctr Ageing Dementia Res, Brisbane, Qld 4072, Australia
[7] Univ Sydney, Brain & Mind Res Inst, Camperdown, NSW 2050, Australia
基金
澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会; 英国医学研究理事会;
关键词
AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DEGENERATION; ANTI-TAU ANTIBODIES; ONE-STEP GENERATION; TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; REPEAT EXPANSION; HEXANUCLEOTIDE REPEAT; ALZHEIMERS-DISEASE;
D O I
10.1038/nrneurol.2015.65
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are related neurodegenerative disorders, which are characterized by a rapid decline in cognitive and motor functions, and short survival. Although the clinical and neuropathological characterization of these diseases has progressed-in part-through animal studies of pathogenetic mechanisms, the translation of findings from rodent models to clinical practice has generally not been successful. This article discusses the gap between preclinical animal studies in mice and clinical trials in patients with FTD or ALS. We outline how to better design preclinical studies, and present strategies to improve mouse models to overcome the translational shortfall. This new approach could help identify drugs that are more likely to achieve a therapeutic benefit for patients.
引用
收藏
页码:360 / 366
页数:7
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