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FTD and ALS—translating mouse studies into clinical trials

Nature Reviews Neurology volume 11, pages 360–366 (2015)Cite this article

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Abstract

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.

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Figure 1: Current clinical trials in FTD and ALS.

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Acknowledgements

This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council of Australia (NHMRC) programme grant (#1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Node (#CE110001021). In addition, the group received project funding from NHMRC (#1020562, #1081916), ARC (#DP130102027) and MND Australia. L.M.I. is an NHMRC Senior Research Fellow (#1003083) and G.M.H. is an NHMRC Senior Principal Research Fellow (#630434).

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Authors and Affiliations

  1. Dementia Research Unit, School of Medical Sciences, Wallace Wurth Building East, The University of New South Wales, Sydney, 2052, NSW, Australia

    Lars M. Ittner

  2. The University of New South Wales and Neuroscience Research Australia, Margarete Ainsworth Building, Barker Street, Sydney, 2031, NSW, Australia

    Glenda M. Halliday & John R. Hodges

  3. Disciplines of Medicine and Pathology, Sydney Medical School, Edward Ford Building A27, The University of Sydney, Sydney, 2006, NSW, Australia

    Jillian J. Kril

  4. Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building #79, Brisbane, 4072, QLD, Australia

    Jürgen Götz

  5. Brain and Mind Research Institute, The University of Sydney, 94 Mallett Street, Camperdown, 2050, NSW, Australia

    Matthew C. Kiernan

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  1. Lars M. Ittner
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  2. Glenda M. Halliday
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  4. Jürgen Götz
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  6. Matthew C. Kiernan
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The authors contributed equally to this manuscript.

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Correspondence to Lars M. Ittner.

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Ittner, L., Halliday, G., Kril, J. et al. FTD and ALS—translating mouse studies into clinical trials. Nat Rev Neurol 11, 360–366 (2015). https://doi.org/10.1038/nrneurol.2015.65

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