{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:59:06Z","timestamp":1791233946477,"version":"4.1.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","prd-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Parkinsonism & Related Disorders"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.parkreldis.2026.108998","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:13:47Z","timestamp":1790147627000},"page":"108998","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hope or hype: novel disease-modifying treatments for Huntington disease"],"prefix":"10.1016","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1492-5237","authenticated-orcid":false,"given":"Surabhi","family":"Garg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-7479","authenticated-orcid":false,"given":"Tiago A.","family":"Mestre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.parkreldis.2026.108998_bib1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41582-025-01159-7","article-title":"Huntington disease: somatic expansion, pathobiology and therapeutics","volume":"22","author":"Donaldson","year":"2026","journal-title":"Nat. Rev. Neurol."},{"issue":"8","key":"10.1016\/j.parkreldis.2026.108998_bib2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11910-024-01345-y","article-title":"Huntington's disease: latest frontiers in therapeutics","volume":"24","author":"Saade","year":"2024","journal-title":"Curr. Neurol. Neurosci. Rep."},{"issue":"2","key":"10.1016\/j.parkreldis.2026.108998_bib3","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s13311-012-0112-2","article-title":"Huntington's disease and the striatal medium spiny neuron: Cell-autonomous and non-cell-autonomous mechanisms of disease","volume":"9","author":"Ehrlich","year":"2012","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.parkreldis.2026.108998_bib4","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"issue":"4","key":"10.1016\/j.parkreldis.2026.108998_bib5","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/ng0893-398","article-title":"The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease","volume":"4","author":"Andrew","year":"1993","journal-title":"Nat. Genet."},{"issue":"5","key":"10.1016\/j.parkreldis.2026.108998_bib6","first-page":"1202","article-title":"The likelihood of being affected with huntington disease by a particular age, for a specific CAG size","volume":"60","author":"Brinkman","year":"1997","journal-title":"Am. J. Hum. Genet."},{"issue":"3","key":"10.1016\/j.parkreldis.2026.108998_bib7","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.neuron.2025.01.008","article-title":"Somatic CAG-repeat expansion drives neuronal loss in Huntington's disease","volume":"113","author":"Bates","year":"2025","journal-title":"Neuron"},{"issue":"7","key":"10.1016\/j.parkreldis.2026.108998_bib8","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S1474-4422(22)00120-X","article-title":"A biological classification of Huntington's disease: the integrated staging system","volume":"21","author":"Tabrizi","year":"2022","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.1016\/j.parkreldis.2026.108998_bib9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3233\/JHD-240043","article-title":"Refining the language of huntington's disease progression with the huntington's disease integrated staging system (HD-ISS)","volume":"13","author":"Sampaio","year":"2024","journal-title":"J. Huntingt. Dis."},{"issue":"1","key":"10.1016\/j.parkreldis.2026.108998_bib10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3233\/JHD-220555","article-title":"Applying the huntington's disease integrated staging system (HD-ISS) to observational studies","volume":"12","author":"Long","year":"2023","journal-title":"J. Huntingt. Dis."},{"issue":"12","key":"10.1016\/j.parkreldis.2026.108998_bib11","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/s00415-025-13409-1","article-title":"Simple diameters, accurate stages:a practical approach to HD-ISS staging","volume":"272","author":"Heim","year":"2025","journal-title":"J. Neurol."},{"key":"10.1016\/j.parkreldis.2026.108998_bib12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.coph.2015.07.005","article-title":"An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies","volume":"24","author":"McClorey","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"issue":"6","key":"10.1016\/j.parkreldis.2026.108998_bib13","first-page":"707","article-title":"Oligonucleotide therapeutics in neurodegenerative diseases","volume":"15","author":"Scoles","year":"2018","journal-title":"RNA Biol."},{"issue":"7","key":"10.1016\/j.parkreldis.2026.108998_bib14","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1136\/jmg.38.7.450","article-title":"Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease","volume":"38","author":"Ho","year":"2001","journal-title":"J. Med. Genet."},{"issue":"2","key":"10.1016\/j.parkreldis.2026.108998_bib15","first-page":"105","article-title":"Antisense oligonucleotide therapy: from design to the huntington disease clinic","volume":"36","author":"Rook","year":"2022","journal-title":"BioDrugs Clin. Immunother. Biopharm. Gene Ther."},{"issue":"47","key":"10.1016\/j.parkreldis.2026.108998_bib16","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/bi101208k","article-title":"Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat","volume":"49","author":"Gagnon","year":"2010","journal-title":"Biochemistry"},{"issue":"5","key":"10.1016\/j.parkreldis.2026.108998_bib17","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nbt.1539","article-title":"Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs","volume":"27","author":"Hu","year":"2009","journal-title":"Nat. Biotechnol."},{"issue":"24","key":"10.1016\/j.parkreldis.2026.108998_bib18","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1056\/NEJMoa1900907","article-title":"Targeting huntingtin expression in patients with huntington's disease","volume":"380","author":"Tabrizi","year":"2019","journal-title":"N. Engl. J. Med."},{"issue":"23","key":"10.1016\/j.parkreldis.2026.108998_bib19","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1056\/NEJMc2300400","article-title":"Tominersen in adults with manifest huntington's disease","volume":"389","author":"McColgan","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.parkreldis.2026.108998_bib22","series-title":"Roche Ends Two Huntington's Disease Drug Programmes After Disappointing Results \u2013 Hdbuzz [Internet]","year":"2026"},{"key":"10.1016\/j.parkreldis.2026.108998_bib23","unstructured":"Bandara A, Slawek J, Suchowersky O, Reilmann R, Mestre TA, Xu D, et al. SELECT-HD: Evaluating Allele-Selective Mutant Huntingtin Lowering in Huntington's Disease."},{"key":"10.1016\/j.parkreldis.2026.108998_bib28","unstructured":"Vico therapeutics announces patient dosing in twice-annual regimen of VO659 in phase 1\/2 trial in huntington's disease, Spinocerebell. Ataxia Type 3 and Type 1 \u2013 Vico Therapeut. . Available from: https:\/\/vicotx.com\/press-release\/vico-therapeutics-announces-patient-dosing-in-twice-annual-regimen-of-vo659-in-phase-1-2-trial-in-huntingtons-disease-spinocerebellar-ataxia-type-3-and-type-1\/."},{"issue":"4","key":"10.1016\/j.parkreldis.2026.108998_bib29","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s13311-020-00891-w","article-title":"Therapeutic update on huntington's disease: symptomatic treatments and emerging disease-modifying therapies","volume":"17","author":"Dash","year":"2020","journal-title":"Neurotherapeutics"},{"issue":"10","key":"10.1016\/j.parkreldis.2026.108998_bib30","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","article-title":"Therapies targeting DNA and RNA in Huntington's disease","volume":"16","author":"Wild","year":"2017","journal-title":"Lancet Neurol."},{"issue":"8","key":"10.1016\/j.parkreldis.2026.108998_bib31","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1001\/archneurol.2009.180","article-title":"Progress and challenges in RNA interference therapy for huntington disease","volume":"66","author":"Harper","year":"2009","journal-title":"Arch. Neurol."},{"issue":"1","key":"10.1016\/j.parkreldis.2026.108998_bib32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1177\/18796397251399751","article-title":"Huntington's disease clinical trials update: october 2025","volume":"15","author":"Farag","year":"2026","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.parkreldis.2026.108998_bib34","article-title":"A new hope for patients with huntington's disease?","volume":"88","year":"2025","journal-title":"EClinicalMedicine"},{"key":"10.1016\/j.parkreldis.2026.108998_bib35","author":"Wild"},{"key":"10.1016\/j.parkreldis.2026.108998_bib36","unstructured":"FDA demands phase 3 trial of uniqure's Huntington's gene therapy [Internet]. [cited 2026 May 23]. Available from: https:\/\/www.fiercebiotech.com\/biotech\/uniqure-shares-crash-40-fda-rejects-early-approval-path-huntingtons-gene-therapy?utm_source=chatgpt.com."},{"key":"10.1016\/j.parkreldis.2026.108998_bib37","unstructured":"Uniqure Announces Positive Topline Results from Pivotal Phase I\/II Study of AMT-130 in Patients with Huntington's Disease | uniqure BV [Internet]. [cited 2026 May 23]. Available from: https:\/\/uniqure.gcs-web.com\/news-releases\/news-release-details\/uniqure-announces-positive-topline-results-pivotal-phase-iii?utm_source=chatgpt.com."},{"key":"10.1016\/j.parkreldis.2026.108998_bib38","unstructured":"Uniqure Provides Regulatory Update on AMT-130 for Huntington's Disease | uniqure BV [Internet]. [cited 2026 May 23]. Available from: https:\/\/uniqure.gcs-web.com\/news-releases\/news-release-details\/uniqure-provides-regulatory-update-amt-130-huntingtons-disease-2?utm_source=chatgpt.com."},{"key":"10.1016\/j.parkreldis.2026.108998_bib40","series-title":"FDA allows AMT-130 huntington disease data to support planned BLA submission under accelerated approval pathway","author":"Pasculli","year":"2026"},{"key":"10.1016\/j.parkreldis.2026.108998_bib43","doi-asserted-by":"crossref","unstructured":"J001 preliminary results from the first-in-human study of ER2001, an innovative treatment for Huntington's disease using in vivo self-assembled sirna | J. Neurol. Neurosurg. & Psychiatr. .2024;95(Suppl 1):A1\u2013A193 Available from: https:\/\/jnnp.bmj.com\/content\/95\/Suppl_1\/A157.3.","DOI":"10.1136\/jnnp-2024-EHDN.322"},{"key":"10.1016\/j.parkreldis.2026.108998_bib45","unstructured":"Sarepta Therapeutics Announces Approval of Clinical Trial Application for SRP-1005, Its Investigational Treatment for Huntington's Disease | Sarepta Therapeutics, Inc. [Internet]. [cited 2026 September 13]. Available from: https:\/\/investorrelations.sarepta.com\/news-releases\/news-release-details\/sarepta-therapeutics-announces-approval-clinical-trial."},{"issue":"1","key":"10.1016\/j.parkreldis.2026.108998_bib46","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/s41467-022-28653-6","article-title":"An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion","volume":"13","author":"Keller","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.parkreldis.2026.108998_bib47","series-title":"Conference","year":"2019"},{"issue":"12","key":"10.1016\/j.parkreldis.2026.108998_bib48","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.1093\/nar\/gkad259","article-title":"Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy","volume":"51","author":"Ottesen","year":"2023","journal-title":"Pract. Nucleic Acids Res."},{"key":"10.1016\/j.parkreldis.2026.108998_bib50","unstructured":"Huntington's Disease Youth Organization - Novartis Announces INVEST-HD [Internet]. [cited 2026 May 23]. Available from: https:\/\/www.hdyo.org\/a\/900-novartis-announces-invest-hd."},{"issue":"5","key":"10.1016\/j.parkreldis.2026.108998_bib52","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1093\/brain\/awae063","article-title":"A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease","volume":"147","author":"Aldous","year":"2024","journal-title":"Brain J. Neurol."},{"issue":"4","key":"10.1016\/j.parkreldis.2026.108998_bib53","article-title":"Huntington's disease in the era of somatic instability, biomarkers, and targeted therapies: a narrative review","volume":"78","author":"Cervantes-Arriaga","year":"2026","journal-title":"Rev Investig Cl\u00ednica"},{"issue":"6","key":"10.1016\/j.parkreldis.2026.108998_bib54","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/s41588-025-02191-5","article-title":"Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease highlight shared and tissue-specific effects","volume":"57","year":"2025","journal-title":"Nat. Genet."},{"issue":"6","key":"10.1016\/j.parkreldis.2026.108998_bib55","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.cell.2025.01.031","article-title":"Distinct mismatch-repair complex genes set neuronal CAG-repeat expansion rate to drive selective pathogenesis in HD mice","volume":"188","author":"Wang","year":"2025","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.parkreldis.2026.108998_bib56","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/j.ymthe.2023.05.006","article-title":"Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington's disease","volume":"31","author":"O'Reilly","year":"2023","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"issue":"785","key":"10.1016\/j.parkreldis.2026.108998_bib57","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adn4600","article-title":"Antisense oligonucleotide-mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington's disease iPSC-derived striatal neurons","volume":"17","author":"Bunting","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.parkreldis.2026.108998_bib58","unstructured":"Skyhawk therapeutics announces first patient dosed in phase 2\/3 FALCON-HD trial of SKY-0515 for huntington's disease [Internet]. [cited 2026 May 23]. Available from: https:\/\/www.prnewswire.com\/news-releases\/skyhawk-therapeutics-announces-first-patient-dosed-in-phase-23-falcon-hd-trial-of-sky-0515-for-huntingtons-disease-302483907.html."},{"key":"10.1016\/j.parkreldis.2026.108998_bib59","author":"Falcon"},{"issue":"3","key":"10.1016\/j.parkreldis.2026.108998_bib61","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41591-024-03424-6","article-title":"Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis","volume":"31","author":"Scahill","year":"2025","journal-title":"Nat. Med."},{"issue":"7","key":"10.1016\/j.parkreldis.2026.108998_bib62","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1474-4422(22)00121-1","article-title":"Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities","volume":"21","author":"Tabrizi","year":"2022","journal-title":"Lancet Neurol."},{"issue":"16","key":"10.1016\/j.parkreldis.2026.108998_bib63","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241613021","article-title":"From pathogenesis to therapeutics: a review of 150 years of huntington's disease research","volume":"24","author":"Jiang","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"12","key":"10.1016\/j.parkreldis.2026.108998_bib64","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1093\/brain\/awac241","article-title":"Alternative processing of human HTT mRNA with implications for Huntington's disease therapeutics","volume":"145","author":"Fienko","year":"2022","journal-title":"Brain"}],"container-title":["Parkinsonism & Related Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1353802026008254?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1353802026008254?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:25:45Z","timestamp":1791231945000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1353802026008254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":50,"alternative-id":["S1353802026008254"],"URL":"https:\/\/doi.org\/10.1016\/j.parkreldis.2026.108998","relation":{},"ISSN":["1353-8020"],"issn-type":[{"value":"1353-8020","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hope or hype: novel disease-modifying treatments for Huntington disease","name":"articletitle","label":"Article Title"},{"value":"Parkinsonism & Related Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.parkreldis.2026.108998","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108998"}}