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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 470-478 |
| Number of pages | 9 |
| Journal | Movement Disorders |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- GSK-3
- Pharmacological treatment
- Progressive supranuclear palsy
- Randomized controlled clinical trial
- Tideglusib
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Medicine(all)
Cite this
A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. / Tolosa, Eduardo; Litvan, Irene; Höglinger, Günter U.; Burn, David; Lees, Andrew; Andrés, María V.; Gómez-Carrillo, Belén; León, Teresa; Del Ser, Teodoro; Gómez, J. C.; Tijero, B.; Berganzo, K.; García de Yebenes, J.; Lopez Sendón, J. L.; Garcia, G.; Tolosa, E.; Buongiorno, M. T.; Bargalló, N.; Burguera, J. A.; Martinez, I.; Ruiz-Martínez, J.; Narrativel, I.; Vivancos, F.; Ybot, I.; Aguilar, M.; Quilez, P.; Boada, M.; Lafuente, A.; Hernandez, I.; López-Lozano, J. J.; Mata, M.; Kupsch, A.; Lipp, A.; Ebersbach, G.; Schmidt, T.; Hahn, K.; Höglinger, G.; Höllerhage, M.; Oertel, W. H.; Respondek, G.; Stamelou, M.; Reichmann, H.; Wolz, M.; Schneider, C.; Klingelhöfer, L.; Berg, D.; Maetzler, W.; Srulijes, K. K.; Ludolph, A.; Kassubek, J.; Steiger, M.; Tyler, K.; Burn, D. J.; Morris, L.; Lees, A.; Ling, H.; Hauser, R.; McClain, T.; Truong, D.; Jenkins, S.; Litvan, I.; Houghton, D.; Ferrara, J.; Bordelon, Y.; Gratiano, A.; Golbe, L.; Mark, M.; Uitti, R.; Ven Gerpen, J.
In: Movement Disorders, Vol. 29, No. 4, 2014, p. 470-478.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy
AU - Tolosa, Eduardo
AU - Litvan, Irene
AU - Höglinger, Günter U.
AU - Burn, David
AU - Lees, Andrew
AU - Andrés, María V.
AU - Gómez-Carrillo, Belén
AU - León, Teresa
AU - Del Ser, Teodoro
AU - Gómez, J. C.
AU - Tijero, B.
AU - Berganzo, K.
AU - García de Yebenes, J.
AU - Lopez Sendón, J. L.
AU - Garcia, G.
AU - Tolosa, E.
AU - Buongiorno, M. T.
AU - Bargalló, N.
AU - Burguera, J. A.
AU - Martinez, I.
AU - Ruiz-Martínez, J.
AU - Narrativel, I.
AU - Vivancos, F.
AU - Ybot, I.
AU - Aguilar, M.
AU - Quilez, P.
AU - Boada, M.
AU - Lafuente, A.
AU - Hernandez, I.
AU - López-Lozano, J. J.
AU - Mata, M.
AU - Kupsch, A.
AU - Lipp, A.
AU - Ebersbach, G.
AU - Schmidt, T.
AU - Hahn, K.
AU - Höglinger, G.
AU - Höllerhage, M.
AU - Oertel, W. H.
AU - Respondek, G.
AU - Stamelou, M.
AU - Reichmann, H.
AU - Wolz, M.
AU - Schneider, C.
AU - Klingelhöfer, L.
AU - Berg, D.
AU - Maetzler, W.
AU - Srulijes, K. K.
AU - Ludolph, A.
AU - Kassubek, J.
AU - Steiger, M.
AU - Tyler, K.
AU - Burn, D. J.
AU - Morris, L.
AU - Lees, A.
AU - Ling, H.
AU - Hauser, R.
AU - McClain, T.
AU - Truong, D.
AU - Jenkins, S.
AU - Litvan, I.
AU - Houghton, D.
AU - Ferrara, J.
AU - Bordelon, Y.
AU - Gratiano, A.
AU - Golbe, L.
AU - Mark, M.
AU - Uitti, R.
AU - Ven Gerpen, J.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - GSK-3
KW - Pharmacological treatment
KW - Progressive supranuclear palsy
KW - Randomized controlled clinical trial
KW - Tideglusib
UR - http://www.scopus.com/inward/record.url?scp=84898056918&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898056918&partnerID=8YFLogxK
U2 - 10.1002/mds.25824
DO - 10.1002/mds.25824
M3 - Article
C2 - 24532007
AN - SCOPUS:84898056918
VL - 29
SP - 470
EP - 478
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 4
ER -