Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial.
Identifieur interne : 000375 ( Main/Exploration ); précédent : 000374; suivant : 000376Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial.
Auteurs : Günter U. Höglinger [Allemagne] ; Hans-Jürgen Huppertz ; Stefan Wagenpfeil ; María V. Andrés ; Vincente Belloch ; Teresa Le N ; Teodoro Del SerSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Atrophy (drug therapy), Atrophy (pathology), Brain (drug effects), Brain (pathology), Disease Progression, Double-Blind Method, Enzyme Inhibitors (pharmacology), Enzyme Inhibitors (therapeutic use), Female, Glycogen Synthase Kinase 3 (antagonists & inhibitors), Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size (drug effects), Supranuclear Palsy, Progressive (drug therapy), Supranuclear Palsy, Progressive (pathology), Thiadiazoles (pharmacology), Thiadiazoles (therapeutic use).
- MESH :
- chemical , antagonists & inhibitors : Glycogen Synthase Kinase 3.
- chemical , pharmacology : Enzyme Inhibitors, Thiadiazoles.
- drug effects : Brain, Organ Size.
- drug therapy : Atrophy, Supranuclear Palsy, Progressive.
- pathology : Atrophy, Brain, Supranuclear Palsy, Progressive.
- chemical , therapeutic use : Enzyme Inhibitors, Thiadiazoles.
- Aged, Aged, 80 and over, Disease Progression, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged.
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.
DOI: 10.1002/mds.25815
PubMed: 24488721
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">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.</div>
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<name sortKey="Del Ser, Teodoro" sort="Del Ser, Teodoro" uniqKey="Del Ser T" first="Teodoro" last="Del Ser">Teodoro Del Ser</name>
<name sortKey="Huppertz, Hans Jurgen" sort="Huppertz, Hans Jurgen" uniqKey="Huppertz H" first="Hans-Jürgen" last="Huppertz">Hans-Jürgen Huppertz</name>
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