FTD and ALS--translating mouse studies into clinical trials.
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.
Dementia Research Unit, School of Medical Sciences, Wallace Wurth Building East, The University of New South Wales, Sydney, NSW 2052, Australia.
Lars M
LM
Ittner
The University of New South Wales and Neuroscience Research Australia, Margarete Ainsworth Building, Barker Street, Sydney, NSW 2031, Australia.
Glenda M
GM
Halliday
Disciplines of Medicine and Pathology, Sydney Medical School, Edward Ford Building A27, The University of Sydney, Sydney, NSW 2006, Australia.
Jillian J
JJ
Kril
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building #79, Brisbane, QLD 4072, Australia.
Jürgen
J
Götz
The University of New South Wales and Neuroscience Research Australia, Margarete Ainsworth Building, Barker Street, Sydney, NSW 2031, Australia.
John R
JR
Hodges
Brain and Mind Research Institute, The University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
Matthew C
MC
Kiernan
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D057180:Frontotemporal Dementia / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D051379:Mice; D057170:Translational Research, Biomedical