Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy

Michael Gold1, Stefan Lorenzl2, Alistair J Stewart1, Bruce H Morimoto1, David R Williams3, Illana Gozes1,41Allon Therapeutics Inc, Vancouver, BC, Canada; 2Interdisciplinary Center for Palliative Medicine, Munich University Hospital Klinikum Grosshadern, Munich, Germany; 3Van Cleef/Roet Centre for Ne...

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Autores principales:	Gozes I, Williams DR, Morimoto BH, Stewart AJ, Lorenzl S, Gold M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/ec9d991512034ae7beea5a6b53c6d6e6
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spelling	oai:doaj.org-article:ec9d991512034ae7beea5a6b53c6d6e62021-12-02T03:56:19ZCritical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy1176-63281178-2021https://doaj.org/article/ec9d991512034ae7beea5a6b53c6d6e62012-02-01T00:00:00Zhttp://www.dovepress.com/critical-appraisal-of-the-role-of-davunetide-in-the-treatment-of-progr-a9228https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Michael Gold1, Stefan Lorenzl2, Alistair J Stewart1, Bruce H Morimoto1, David R Williams3, Illana Gozes1,41Allon Therapeutics Inc, Vancouver, BC, Canada; 2Interdisciplinary Center for Palliative Medicine, Munich University Hospital Klinikum Grosshadern, Munich, Germany; 3Van Cleef/Roet Centre for Nervous Diseases, Monash University, Melbourne, Australia; 4The 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, IsraelAbstract: 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&#39;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.Keywords: tau protein aggregates, neurodegenerative, neurofibrillary tanglesGozes IWilliams DRMorimoto BHStewart AJLorenzl SGold MDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2012, Iss default, Pp 85-93 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Gozes I Williams DR Morimoto BH Stewart AJ Lorenzl S Gold M Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
description	Michael Gold1, Stefan Lorenzl2, Alistair J Stewart1, Bruce H Morimoto1, David R Williams3, Illana Gozes1,41Allon Therapeutics Inc, Vancouver, BC, Canada; 2Interdisciplinary Center for Palliative Medicine, Munich University Hospital Klinikum Grosshadern, Munich, Germany; 3Van Cleef/Roet Centre for Nervous Diseases, Monash University, Melbourne, Australia; 4The 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, IsraelAbstract: 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&#39;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.Keywords: tau protein aggregates, neurodegenerative, neurofibrillary tangles
format	article
author	Gozes I Williams DR Morimoto BH Stewart AJ Lorenzl S Gold M
author_facet	Gozes I Williams DR Morimoto BH Stewart AJ Lorenzl S Gold M
author_sort	Gozes I
title	Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
title_short	Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
title_full	Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
title_fullStr	Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
title_full_unstemmed	Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
title_sort	critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/ec9d991512034ae7beea5a6b53c6d6e6
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Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy

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