A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy.
Identifieur interne : 000683 ( Main/Exploration ); précédent : 000682; suivant : 000684A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy.
Auteurs : Eduardo Tolosa [Espagne] ; Irene Litvan ; Günter U. Höglinger ; David Burn ; Andrew Lees ; María V. Andrés ; Belén G Mez-Carrillo ; Teresa Le N ; Teodoro Del SerSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Activities of Daily Living, Aged, Cognition (drug effects), Double-Blind Method, Enzyme Inhibitors (adverse effects), Enzyme Inhibitors (pharmacology), Enzyme Inhibitors (therapeutic use), Female, Glycogen Synthase Kinase 3 (antagonists & inhibitors), Humans, Male, Middle Aged, Motor Activity (drug effects), Supranuclear Palsy, Progressive (drug therapy), Thiadiazoles (adverse effects), Thiadiazoles (pharmacology), Thiadiazoles (therapeutic use), Treatment Outcome.
- MESH :
- chemical , adverse effects : Enzyme Inhibitors, Thiadiazoles.
- chemical , antagonists & inhibitors : Glycogen Synthase Kinase 3.
- drug effects : Cognition, Motor Activity.
- drug therapy : Supranuclear Palsy, Progressive.
- chemical , pharmacology : Enzyme Inhibitors, Thiadiazoles.
- chemical , therapeutic use : Enzyme Inhibitors, Thiadiazoles.
- Activities of Daily Living, Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Treatment Outcome.
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.
DOI: 10.1002/mds.25824
PubMed: 24532007
Affiliations:
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Andrés</name></author><author><name sortKey="G Mez Carrillo, Belen" sort="G Mez Carrillo, Belen" uniqKey="G Mez Carrillo B" first="Belén" last="G Mez-Carrillo">Belén G Mez-Carrillo</name></author><author><name sortKey="Le N, Teresa" sort="Le N, Teresa" uniqKey="Le N T" first="Teresa" last="Le N">Teresa Le N</name></author><author><name sortKey="Del Ser, Teodoro" sort="Del Ser, Teodoro" uniqKey="Del Ser T" first="Teodoro" last="Del Ser">Teodoro Del Ser</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24532007</idno><idno type="pmid">24532007</idno><idno type="doi">10.1002/mds.25824</idno><idno type="wicri:Area/PubMed/Corpus">000580</idno><idno type="wicri:Area/PubMed/Curation">000580</idno><idno type="wicri:Area/PubMed/Checkpoint">000703</idno><idno type="wicri:Area/Ncbi/Merge">003F17</idno><idno type="wicri:Area/Ncbi/Curation">003F17</idno><idno type="wicri:Area/Ncbi/Checkpoint">003F17</idno><idno type="wicri:Area/Main/Merge">000683</idno><idno type="wicri:Area/Main/Curation">000683</idno><idno type="wicri:Area/Main/Exploration">000683</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy.</title><author><name sortKey="Tolosa, Eduardo" sort="Tolosa, Eduardo" uniqKey="Tolosa E" first="Eduardo" last="Tolosa">Eduardo Tolosa</name><affiliation wicri:level="3"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>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</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Litvan, Irene" sort="Litvan, Irene" uniqKey="Litvan I" first="Irene" last="Litvan">Irene Litvan</name></author><author><name sortKey="Hoglinger, Gunter U" sort="Hoglinger, Gunter U" uniqKey="Hoglinger G" first="Günter U" last="Höglinger">Günter U. Höglinger</name></author><author><name sortKey="Burn, David" sort="Burn, David" uniqKey="Burn D" first="David" last="Burn">David Burn</name></author><author><name sortKey="Lees, Andrew" sort="Lees, Andrew" uniqKey="Lees A" first="Andrew" last="Lees">Andrew Lees</name></author><author><name sortKey="Andres, Maria V" sort="Andres, Maria V" uniqKey="Andres M" first="María V" last="Andrés">María V. Andrés</name></author><author><name sortKey="G Mez Carrillo, Belen" sort="G Mez Carrillo, Belen" uniqKey="G Mez Carrillo B" first="Belén" last="G Mez-Carrillo">Belén G Mez-Carrillo</name></author><author><name sortKey="Le N, Teresa" sort="Le N, Teresa" uniqKey="Le N T" first="Teresa" last="Le N">Teresa Le N</name></author><author><name sortKey="Del Ser, Teodoro" sort="Del Ser, Teodoro" uniqKey="Del Ser T" first="Teodoro" last="Del Ser">Teodoro Del Ser</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Activities of Daily Living</term><term>Aged</term><term>Cognition (drug effects)</term><term>Double-Blind Method</term><term>Enzyme Inhibitors (adverse effects)</term><term>Enzyme Inhibitors (pharmacology)</term><term>Enzyme Inhibitors (therapeutic use)</term><term>Female</term><term>Glycogen Synthase Kinase 3 (antagonists & inhibitors)</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Motor Activity (drug effects)</term><term>Supranuclear Palsy, Progressive (drug therapy)</term><term>Thiadiazoles (adverse effects)</term><term>Thiadiazoles (pharmacology)</term><term>Thiadiazoles (therapeutic use)</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Enzyme Inhibitors</term><term>Thiadiazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Glycogen Synthase Kinase 3</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cognition</term><term>Motor Activity</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Supranuclear Palsy, Progressive</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term><term>Thiadiazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Enzyme Inhibitors</term><term>Thiadiazoles</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Activities of Daily Living</term><term>Aged</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Espagne</li></country><region><li>Catalogne</li></region><settlement><li>Barcelone</li></settlement></list><tree><noCountry><name sortKey="Andres, Maria V" sort="Andres, Maria V" uniqKey="Andres M" first="María V" last="Andrés">María V. Andrés</name><name sortKey="Burn, David" sort="Burn, David" uniqKey="Burn D" first="David" last="Burn">David Burn</name><name sortKey="Del Ser, Teodoro" sort="Del Ser, Teodoro" uniqKey="Del Ser T" first="Teodoro" last="Del Ser">Teodoro Del Ser</name><name sortKey="G Mez Carrillo, Belen" sort="G Mez Carrillo, Belen" uniqKey="G Mez Carrillo B" first="Belén" last="G Mez-Carrillo">Belén G Mez-Carrillo</name><name sortKey="Hoglinger, Gunter U" sort="Hoglinger, Gunter U" uniqKey="Hoglinger G" first="Günter U" last="Höglinger">Günter U. Höglinger</name><name sortKey="Le N, Teresa" sort="Le N, Teresa" uniqKey="Le N T" first="Teresa" last="Le N">Teresa Le N</name><name sortKey="Lees, Andrew" sort="Lees, Andrew" uniqKey="Lees A" first="Andrew" last="Lees">Andrew Lees</name><name sortKey="Litvan, Irene" sort="Litvan, Irene" uniqKey="Litvan I" first="Irene" last="Litvan">Irene Litvan</name></noCountry><country name="Espagne"><region name="Catalogne"><name sortKey="Tolosa, Eduardo" sort="Tolosa, Eduardo" uniqKey="Tolosa E" first="Eduardo" last="Tolosa">Eduardo Tolosa</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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