title: A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy.
abstract: It is believed that glycogen synthase kinase-3 (GSK-3) hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) study was a double-blind, placebo-controlled, randomized trial to assess the efficacy, safety, and tolerability of tideglusib, a GSK-3 inhibitor, as potential treatment for PSP. The study enrolled 146 PSP patients with mild-to-moderate disease who were randomized to receive once-daily 600 mg tideglusib, 800 mg tideglusib, or placebo (ratio, 2:2:1) administered orally over 52 weeks. The primary endpoint was the change from baseline to week 52 on the PSP rating scale. Secondary endpoints were safety and tolerability of tideglusib, changes in motor function (the Timed Up and Go Test), cognition (Dementia Rating Scale-2, Frontal Assessment Battery, verbal fluency), apathy (Starkstein scale), activities of daily living (Schwab and England scale; Unified Parkinson's Disease Rating Scale, part II), quality of life (EuroQol), and Global Clinical Assessment. Brain atrophy on magnetic resonance imaging and several biomarkers in plasma and cerebrospinal fluid also were examined. No significant differences were detected in the primary or secondary endpoints at week 52 between placebo and either dose of tideglusib. Tideglusib was safe, with the exception of some asymptomatic, transient, and reversible transaminase elevations (mainly alanine aminotransferase) in 9% of patients, and diarrhea in 13% of patients. Tideglusib was generally well tolerated but it did not show clinical efficacy in patients with mild-to-moderate PSP.
authors: Neurology Service, Hospital Clinic de Barcelona, Universidad de Barcelona, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors: Eduardo
authors: E
authors: Tolosa
authors: Irene
authors: I
authors: Litvan
authors: Günter U
authors: GU
authors: Höglinger
authors: David
authors: D
authors: Burn
authors: Andrew
authors: A
authors: Lees
authors: María V
authors: MV
authors: Andrés
authors: Belén
authors: B
authors: Gómez-Carrillo
authors: Teresa
authors: T
authors: León
authors: Teodoro
authors: T
authors: Del Ser
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D013494:Supranuclear Palsy, Progressive / Q000188:drug therapy*; D013830:Thiadiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D013830:Thiadiazoles; D038362:Glycogen Synthase Kinase 3; C520571:tideglusib
keywords: GSK-3; pharmacological treatment; progressive supranuclear palsy; randomized controlled clinical trial; tideglusib