{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:42:37Z","timestamp":1790959357124,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T00:00:00Z","timestamp":1410480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2014,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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\u2010in 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\u2010development 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\u2010HD and PREDICT\u2010HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q\u2010Motor) 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\u2010of\u2010concept 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. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26021","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T07:10:44Z","timestamp":1410505844000},"page":"1419-1428","source":"Crossref","is-referenced-by-count":48,"title":["Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches"],"prefix":"10.1002","volume":"29","author":[{"given":"Cristina","family":"Sampaio","sequence":"first","affiliation":[{"name":"CHDI Management\/CHDI Foundation Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Borowsky","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Reilmann","sequence":"additional","affiliation":[{"name":"George Huntington Institute Technology Park Muenster Muenster Germany"},{"name":"Department of Neurodegenerative Diseases and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23953"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.24"},{"key":"e_1_2_8_5_1","volume-title":"Regulation EC N 1394\/2007 of the European Parliament and of The Council of 13 Nivember 2007 on advanced therapies medicinal products","author":"European Comission","year":"2007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70233-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25362"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25559"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70276-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70170-X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182020123"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2013.11.007"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.2.JNS131722"},{"key":"e_1_2_8_15_1","unstructured":"U.S. Food and Drug Administration. Overview of device regulation. 2014. Available at:http:\/\/wwwfdagov\/MedicalDevices\/DeviceRegulationandGuidance\/Overview\/defaulthtm."},{"key":"e_1_2_8_16_1","unstructured":"VesperJ. A prospective pilot trial for pallidal deep brain stimulation in Huntington's disease. 2014.http:\/\/chdifoundationorg\/2014\u2010conference\/."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2786"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.12.020"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt269"},{"key":"e_1_2_8_20_1","unstructured":"ALZFORUM. PBT2.http:\/\/wwwalzforumorg\/therapeutics\/pbt2_br. Accessed 23 July 2014."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.36.8.1099"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.11.023"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099520"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27607"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.02.003"},{"key":"e_1_2_8_26_1","volume-title":"Raptor Pharmaceuticals announces phase 2\/3 clinical trial results with cysteamine (RP103) in Huntington's disease","author":"Raptor Pharmaceuticals","year":"2014"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu010"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-303524.172"},{"issue":"10","key":"e_1_2_8_29_1","first-page":"S47","article-title":"Safety and tolerability of selisistat for the treatment of Huntington's disease: results from a randomized, double\u2010blind, placebo\u2010controlled phase II trial (S47.004)","volume":"82","author":"Reilmann R","year":"2014","journal-title":"Neurology"},{"key":"e_1_2_8_30_1","first-page":"458","article-title":"PDE10A inhibitors: an assessment of the current CNS drug discovery landscape","volume":"12","author":"Chappie T","year":"2009","journal-title":"Curr Opin Drug Discov Devel"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.173294"},{"key":"e_1_2_8_32_1","volume-title":"2013. Study evaluating the safety, tolerability and brain function of 2 doses of PF\u20100254920 In subjects with early Huntington's disease","author":"Pfizer"},{"key":"e_1_2_8_33_1","volume-title":"FDA grants fast track designation to Omeros' OMS824 Huntington's disease program","author":"Omeros","year":"2014"},{"key":"e_1_2_8_34_1","volume-title":"Omeros begins dosing in second phase II study of OMS824 in Huntington's Disease","author":"Omeros","year":"2014"},{"key":"e_1_2_8_35_1","unstructured":"Pharmaceuticals Auspex. SD\u2010809: a VMAT\u20102 inhibitor for the agram (phase 3 ongoing).http:\/\/www.auspexpharma.com\/pipeline\/. Accessed July 2014."},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","unstructured":"Aronin N and DiFiglia M. Huntingtin\u2010LoweringStrategies inHuntington'sDisease:AntisenseOligonucleotides SmallRNAs andGeneEditing. Mov Disord2014;29:1455\u20101461.","DOI":"10.1002\/mds.26020"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70061-9"},{"key":"e_1_2_8_38_1","unstructured":"ISIS\u2010ROCHE. Roche and Isis Pharmaceuticals form alliance for Huntington's Disease. 2013.http:\/\/www.roche.com\/research_and_development\/partnering\/partnering-media\/partnering_news-2013-04-08.htm consulted June 2014."},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","unstructured":"Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington Disease. Neurology 2006;66(3):366-372.","DOI":"10.1212\/01.wnl.0000198586.85250.13"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029522"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1184"},{"key":"e_1_2_8_42_1","first-page":"CD006456","article-title":"Therapeutic interventions for symptomatic treatment in Huntington's disease","volume":"3","author":"Mestre T","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21181"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.05.025"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-79"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000187"},{"key":"e_1_2_8_47_1","unstructured":"Banner Alzheimer Institute. Groundbreaking Alzheimer's disease prevention trial announced. 2012.http:\/\/banneralz.org\/api-news-items\/banner-alzheimers-partners-with-novartis.aspx consulted June 2014."},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.1.1"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.31.10.1333"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110204"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110204"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130609"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23816"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23243"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23300"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21449"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-301732"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-301940"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25964"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23574"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.11030057"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.26021","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.26021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:06:13Z","timestamp":1760958373000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.26021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,12]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,9,15]]}},"alternative-id":["10.1002\/mds.26021"],"URL":"https:\/\/doi.org\/10.1002\/mds.26021","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,12]]}}}