Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.
Identifieur interne : 000639 ( Main/Exploration ); précédent : 000638; suivant : 000640Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.
Auteurs : Cristina Sampaio [États-Unis] ; Beth Borowsky ; Ralf ReilmannSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- methods : Clinical Trials as Topic, Deep Brain Stimulation, Drug Discovery.
- statistics & numerical data : PubMed.
- therapy : Huntington Disease.
- Humans, Outcome Assessment (Health Care).
Abstract
Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field.
DOI: 10.1002/mds.26021
PubMed: 25216371
Affiliations:
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Le document en format XML
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Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>New Jersey</li></region></list><tree><noCountry><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name></noCountry><country name="États-Unis"><region name="New Jersey"><name sortKey="Sampaio, Cristina" sort="Sampaio, Cristina" uniqKey="Sampaio C" first="Cristina" last="Sampaio">Cristina Sampaio</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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