Pharmacologic Approaches to the Treatment of Huntington's Disease
Identifieur interne : 000102 ( PascalFrancis/Checkpoint ); précédent : 000101; suivant : 000103Pharmacologic Approaches to the Treatment of Huntington's Disease
Auteurs : Charles S. Venuto [États-Unis] ; Andrew Mcgarry [États-Unis] ; QING MA [États-Unis] ; Karl Kieburtz [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2012.
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Abstract
Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder characterized by chorea, cognitive impairment, and behavioral disturbances. Despite advances in diagnosis and improved understanding of HD, treatment remains difficult due to challenging symptoms and a paucity of approved therapeutic interventions. Nonpharmacologic and pharmacologic strategies have been evaluated; regarding the latter, over 80 agents of various classes have been investigated in clinical trials or examined in case reports. Symptomatic treatment, however, is generally confined to antidopaminergic agents for motor dysfunction and antidepressants for mood disorders, while treatment for cognitive dysfunction remains vacant. Several different mechanisms to modify symptoms and disease progression have been targeted in clinical trials. This article reviews some of the more common pharmacologic treatments used for HD, discusses data regarding suboptimal agents that have been tested, and surveys treatments under investigation.
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Venuto</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Mcgarry, Andrew" sort="Mcgarry, Andrew" uniqKey="Mcgarry A" first="Andrew" last="Mcgarry">Andrew Mcgarry</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Qing Ma" sort="Qing Ma" uniqKey="Qing Ma" last="Qing Ma">QING MA</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0106476</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0106476 INIST</idno><idno type="RBID">Pascal:12-0106476</idno><idno type="wicri:Area/PascalFrancis/Corpus">000312</idno><idno type="wicri:Area/PascalFrancis/Curation">002A02</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000102</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Pharmacologic Approaches to the Treatment of Huntington's Disease</title><author><name sortKey="Venuto, Charles S" sort="Venuto, Charles S" uniqKey="Venuto C" first="Charles S." last="Venuto">Charles S. Venuto</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Mcgarry, Andrew" sort="Mcgarry, Andrew" uniqKey="Mcgarry A" first="Andrew" last="Mcgarry">Andrew Mcgarry</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Qing Ma" sort="Qing Ma" uniqKey="Qing Ma" last="Qing Ma">QING MA</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Neurology, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Chorea</term><term>Huntington disease</term><term>Hyperkinesia</term><term>Nervous system diseases</term><term>Surgical approach</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chorée de Huntington</term><term>Hyperkinésie</term><term>Syndrome choréique</term><term>Pathologie du système nerveux</term><term>Voie abord</term><term>Traitement</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder characterized by chorea, cognitive impairment, and behavioral disturbances. Despite advances in diagnosis and improved understanding of HD, treatment remains difficult due to challenging symptoms and a paucity of approved therapeutic interventions. Nonpharmacologic and pharmacologic strategies have been evaluated; regarding the latter, over 80 agents of various classes have been investigated in clinical trials or examined in case reports. Symptomatic treatment, however, is generally confined to antidopaminergic agents for motor dysfunction and antidepressants for mood disorders, while treatment for cognitive dysfunction remains vacant. Several different mechanisms to modify symptoms and disease progression have been targeted in clinical trials. This article reviews some of the more common pharmacologic treatments used for HD, discusses data regarding suboptimal agents that have been tested, and surveys treatments under investigation.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>27</s2></fA05><fA06><s2>1</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Pharmacologic Approaches to the Treatment of Huntington's Disease</s1></fA08><fA11 i1="01" i2="1"><s1>VENUTO (Charles S.)</s1></fA11><fA11 i1="02" i2="1"><s1>MCGARRY (Andrew)</s1></fA11><fA11 i1="03" i2="1"><s1>QING MA</s1></fA11><fA11 i1="04" i2="1"><s1>KIEBURTZ (Karl)</s1></fA11><fA14 i1="01"><s1>Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></fA14><fA14 i1="03"><s1>Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences</s1><s2>Buffalo, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neurology, University of Rochester School of Medicine and Dentistry</s1><s2>Rochester, New York</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ></fA14><fA20><s1>31-41</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000508687520050</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>131 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0106476</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder characterized by chorea, cognitive impairment, and behavioral disturbances. Despite advances in diagnosis and improved understanding of HD, treatment remains difficult due to challenging symptoms and a paucity of approved therapeutic interventions. Nonpharmacologic and pharmacologic strategies have been evaluated; regarding the latter, over 80 agents of various classes have been investigated in clinical trials or examined in case reports. Symptomatic treatment, however, is generally confined to antidopaminergic agents for motor dysfunction and antidepressants for mood disorders, while treatment for cognitive dysfunction remains vacant. Several different mechanisms to modify symptoms and disease progression have been targeted in clinical trials. This article reviews some of the more common pharmacologic treatments used for HD, discusses data regarding suboptimal agents that have been tested, and surveys treatments under investigation.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Chorée de Huntington</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Huntington disease</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Corea Huntington</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Hyperkinésie</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Hyperkinesia</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Hiperquinesia</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Syndrome choréique</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Chorea</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Corea síndrome</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Voie abord</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Surgical approach</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Vía abordaje</s0><s5>09</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Traitement</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Treatment</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Tratamiento</s0><s5>10</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Maladie héréditaire</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Genetic disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad hereditaria</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Trouble neurologique</s0><s5>43</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Neurological disorder</s0><s5>43</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Trastorno neurológico</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Trouble de la psychomotricité</s0><s5>44</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Psychomotor disorder</s0><s5>44</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Trastorno psicomotriz</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Mouvement involontaire</s0><s5>45</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Involuntary movement</s0><s5>45</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Movimiento involuntario</s0><s5>45</s5></fC07><fN21><s1>079</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Venuto, Charles S" sort="Venuto, Charles S" uniqKey="Venuto C" first="Charles S." last="Venuto">Charles S. Venuto</name></region><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><name sortKey="Mcgarry, Andrew" sort="Mcgarry, Andrew" uniqKey="Mcgarry A" first="Andrew" last="Mcgarry">Andrew Mcgarry</name><name sortKey="Qing Ma" sort="Qing Ma" uniqKey="Qing Ma" last="Qing Ma">QING MA</name><name sortKey="Qing Ma" sort="Qing Ma" uniqKey="Qing Ma" last="Qing Ma">QING MA</name><name sortKey="Qing Ma" sort="Qing Ma" uniqKey="Qing Ma" last="Qing Ma">QING MA</name><name sortKey="Venuto, Charles S" sort="Venuto, Charles S" uniqKey="Venuto C" first="Charles S." last="Venuto">Charles S. Venuto</name><name sortKey="Venuto, Charles S" sort="Venuto, Charles S" uniqKey="Venuto C" first="Charles S." last="Venuto">Charles S. 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