Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial

Authors

  • Günter U. Höglinger MD,

    Corresponding author
    1. Department of Neurology, Philipps Universität, Marburg, Germany
    2. Department of Neurology, Technische Universität München, Munich, Germany
    3. German Center for Neurodegenerative Diseases (DZNE), München, Germany
    • Correspondence to: Dr. Günter U. Höglinger, Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), München, Max Lebsche Platz 30, D-81677 Munich, Germany; guenter.hoeglinger@dzne.de

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    • The first two authors contributed equally to this work.

  • Hans-Jürgen Huppertz MD,

    1. Swiss Epilepsy Centre, Zürich, Switzerland
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    • The first two authors contributed equally to this work.

  • Stefan Wagenpfeil PhD,

    1. Institute for Medical Biometry, Epidemiology and Medical Informatics (IMBEI), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
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  • María V Andrés PhD,

    1. Clinical Operations Department, Noscira SA, Madrid, Spain
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  • Vincente Belloch MD,

    1. Scientific Department, Exploraciones Radiológicas Especiales (ERESA), Valencia, Spain
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  • Teresa León MD, PhD,

    1. Clinical Operations Department, Noscira SA, Madrid, Spain
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  • Teodoro del Ser MD,

    1. Medical Department, Noscira SA, Madrid, Spain
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  • for the TAUROS MRI Investigators


  • Funding agencies: This study was funded by Noscira SA, Madrid, Spain. Dr. Höglinger is supported by the Deutsche Forschungsgemeinschaft (DFG, HO2402/6-1).

  • Relevant conflicts of interest/financial disclosures: Three authors were employees of Noscira SA, Madrid, Spain, the company that funded this study.

  • Full financial disclosures and author roles may be found in the online version of this article.

  • Members of the TAUROS MRI Investigators are listed in the Appendix.

ABSTRACT

It is believed that glycogen synthase kinase-3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase-3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double-blind, placebo-controlled trial in patients with mild-to-moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52-week MRI. Automated, observer-independent, atlas-based, and mask-based volumetry was done on high-resolution, T1-weighted, three-dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: −1.3% ± 1.4% vs. −3.1% ± 2.3%, respectively), cerebrum (−1.3% ± 1.5% vs. −3.2% ± 2.1%, respectively), parietal lobe (−1.6% ± 1.9% vs. −4.1% ± 3.0%, respectively), and occipital lobe (−0.3% ± 1.8% vs. −2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society

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