Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
Identifieur interne : 001262 ( Main/Exploration ); précédent : 001261; suivant : 001263Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
Auteurs : Michael Gold [Canada] ; Stefan Lorenzl [Allemagne] ; Alistair J. Stewart [Canada] ; Bruce H. Morimoto [Canada] ; David R. Williams [Australie] ; Illana Gozes [Canada, Israël]Source :
- Neuropsychiatric Disease and Treatment [ 1176-6328 ] ; 2012.
Abstract
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide’s efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.
Url:
DOI: 10.2147/NDT.S12518
PubMed: 22347799
PubMed Central: 3280109
Affiliations:
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Stewart</name><affiliation wicri:level="1"><nlm:aff id="af1-ndt-8-085">Allon Therapeutics Inc, Vancouver, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Allon Therapeutics Inc, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Morimoto, Bruce H" sort="Morimoto, Bruce H" uniqKey="Morimoto B" first="Bruce H" last="Morimoto">Bruce H. Morimoto</name><affiliation wicri:level="1"><nlm:aff id="af1-ndt-8-085">Allon Therapeutics Inc, Vancouver, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Allon Therapeutics Inc, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Williams, David R" sort="Williams, David R" uniqKey="Williams D" first="David R" last="Williams">David R. Williams</name><affiliation wicri:level="1"><nlm:aff id="af3-ndt-8-085">Van Cleef/Roet Centre for Nervous Diseases, Monash University, Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Van Cleef/Roet Centre for Nervous Diseases, Monash University, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="Gozes, Illana" sort="Gozes, Illana" uniqKey="Gozes I" first="Illana" last="Gozes">Illana Gozes</name><affiliation wicri:level="1"><nlm:aff id="af1-ndt-8-085">Allon Therapeutics Inc, Vancouver, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Allon Therapeutics Inc, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-ndt-8-085">The Dr Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Adams Super Center for Brain Studies, and the Department of Human Molecular Genetics and Biochemistry, School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>The Dr Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Adams Super Center for Brain Studies, and the Department of Human Molecular Genetics and Biochemistry, School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv</wicri:regionArea><wicri:noRegion>Tel Aviv</wicri:noRegion></affiliation></author></analytic><series><title level="j">Neuropsychiatric Disease and Treatment</title><idno type="ISSN">1176-6328</idno><idno type="eISSN">1178-2021</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide’s efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Steele, Jc" uniqKey="Steele J">JC Steele</name></author><author><name sortKey="Richardson, Jc" uniqKey="Richardson J">JC Richardson</name></author><author><name sortKey="Olszewski, J" uniqKey="Olszewski J">J Olszewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bensimon, G" uniqKey="Bensimon G">G Bensimon</name></author><author><name sortKey="Ludolph, A" uniqKey="Ludolph A">A Ludolph</name></author><author><name sortKey="Agid, Y" uniqKey="Agid Y">Y Agid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ludolph, Ac" uniqKey="Ludolph A">AC Ludolph</name></author><author><name sortKey="Kassubek, J" uniqKey="Kassubek J">J 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Birdi</name></author><author><name sortKey="Rajput, Ah" uniqKey="Rajput A">AH Rajput</name></author><author><name sortKey="Fenton, M" uniqKey="Fenton M">M Fenton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuiperij, Hb" uniqKey="Kuiperij H">HB Kuiperij</name></author><author><name sortKey="Verbeek, Mm" uniqKey="Verbeek M">MM Verbeek</name></author><author><name sortKey="Borroni, B" uniqKey="Borroni B">B Borroni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kvickstrom, P" uniqKey="Kvickstrom P">P Kvickström</name></author><author><name sortKey="Eriksson, B" uniqKey="Eriksson B">B Eriksson</name></author><author><name sortKey="Van Westen, D" uniqKey="Van Westen D">D van Westen</name></author><author><name sortKey="Latt, J" uniqKey="Latt J">J Latt</name></author><author><name sortKey="Elfgren, C" uniqKey="Elfgren C">C Elfgren</name></author><author><name sortKey="Nilsson, C" uniqKey="Nilsson C">C 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uniqKey="Richardson J">JC Richardson</name></author><author><name sortKey="Steele, J" uniqKey="Steele J">J Steele</name></author><author><name sortKey="Olszewski, J" uniqKey="Olszewski J">J Olszewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maruff, P" uniqKey="Maruff P">P Maruff</name></author><author><name sortKey="Werth, J" uniqKey="Werth J">J Werth</name></author><author><name sortKey="Giordani, B" uniqKey="Giordani B">B Giordani</name></author><author><name sortKey="Caveney, Af" uniqKey="Caveney A">AF Caveney</name></author><author><name sortKey="Feltner, D" uniqKey="Feltner D">D Feltner</name></author><author><name sortKey="Snyder, Pj" uniqKey="Snyder P">PJ Snyder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cubo, E" uniqKey="Cubo E">E Cubo</name></author><author><name sortKey="Stebbins, Gt" uniqKey="Stebbins G">GT Stebbins</name></author><author><name sortKey="Golbe, Li" uniqKey="Golbe L">LI Golbe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Payan, Ca" uniqKey="Payan C">CA Payan</name></author><author><name sortKey="Viallet, F" uniqKey="Viallet F">F Viallet</name></author><author><name sortKey="Landwehrmeyer, Bg" uniqKey="Landwehrmeyer B">BG Landwehrmeyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hensler, M" uniqKey="Hensler M">M Hensler</name></author><author><name sortKey="Paul, S" uniqKey="Paul S">S Paul</name></author><author><name sortKey="Abright, C" uniqKey="Abright C">C Abright</name></author><author><name sortKey="Lorenzl, S" uniqKey="Lorenzl S">S Lorenzl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rickham, Pp" uniqKey="Rickham P">PP Rickham</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>Israël</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li></region><settlement><li>Munich</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Gold, Michael" sort="Gold, Michael" uniqKey="Gold M" first="Michael" last="Gold">Michael Gold</name></noRegion><name sortKey="Gozes, Illana" sort="Gozes, Illana" uniqKey="Gozes I" first="Illana" last="Gozes">Illana Gozes</name><name sortKey="Morimoto, Bruce H" sort="Morimoto, Bruce H" uniqKey="Morimoto B" first="Bruce H" last="Morimoto">Bruce H. Morimoto</name><name sortKey="Stewart, Alistair J" sort="Stewart, Alistair J" uniqKey="Stewart A" first="Alistair J" last="Stewart">Alistair J. Stewart</name></country><country name="Allemagne"><region name="Bavière"><name sortKey="Lorenzl, Stefan" sort="Lorenzl, Stefan" uniqKey="Lorenzl S" first="Stefan" last="Lorenzl">Stefan Lorenzl</name></region></country><country name="Australie"><noRegion><name sortKey="Williams, David R" sort="Williams, David R" uniqKey="Williams D" first="David R" last="Williams">David R. Williams</name></noRegion></country><country name="Israël"><noRegion><name sortKey="Gozes, Illana" sort="Gozes, Illana" uniqKey="Gozes I" first="Illana" last="Gozes">Illana Gozes</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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