References
- Walker FO. Huntington’s disease. Lancet. 2007 Jan 20;369(9557):218–228.
- Frucht S. Phenomenology of chorea. Movement Disorders Phenomenology. Switzerland: Springer; 2020.
- Rawlins MD, Wexler NS, Wexler AR, et al. The prevalence of huntington’s disease. Neuroepidemiology. 2016;46(2):144–153.
- Kwa L, Larson D, Yeh C, et al. Influence of age of onset on huntington’s disease phenotype. Tremor Other Hyperkinet Mov (N Y). 2020 Jul 9;10:21.
- Jimenez-Sanchez M, Licitra F, Underwood BR, et al. Huntington’s disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb Perspect Med. 2017 Jul 5;7(7):a024240.
- Reiner A, Dragatsis I, Dietrich P. Genetics and neuropathology of Huntington’s disease. Int Rev Neurobiol. 2011;98:325–372.
- Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell. 2000 Mar 31;101(1):57–66.
- Marxreiter F, Stemick J, Kohl Z. Huntingtin Lowering Strategies. Int J Mol Sci. 2020 Mar 20;21(6):2146.
- Poplawski GHD, Kawaguchi R, Van Niekerk E, et al. Injured adult neurons regress to an embryonic transcriptional growth state. Nature. 2020 May;581(7806):77–82.
- Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron. 2012 Jun 21;74(6):1031–1044.
- Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, et al. Targeting huntingtin expression in patients with Huntington’s Disease. N Engl J Med. 2019 Jun 13;380(24):2307–2316.
- Roche provides update on tominersen programme in manifest Huntington’s disease [Internet]. 2021; [cited 2021 Mar 22]. Available from: https://www.roche.com/media/releases/med-cor-2021-03-22b.htm
- Promising drug for Huntington disease fails in major trial [Internet]. Science; 2021; [cited 2021 Mar 23]. Available from: https://www.sciencemag.org/news/2021/03/promising-drug-huntington-disease-fails-major-trial
- Wave Life Sciences Highlights Pipeline Progress and Expansion Leveraging New PN Backbone Chemistry Modifications [Internet]. Wave Life Sciences; 2021; January 11, 2021
- Wave Life Sciences Announces Topline Data and Addition of Higher Dose Cohort in Ongoing Phase 1b/2a PRECISION-HD2 Trial in Huntington’s Disease [Internet]. Wave Life Sciences; 2019; December 30, 2019
- Wave Life Sciences Provides Update on Phase 1b/2a PRECISION-HD Trials [Internet]. 2021; [cited 2021 Mar 29]. Available from: https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-provides-update-phase-1b2a-precision-hd
- Datson NA, Gonzalez-Barriga A, Kourkouta E, et al. The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain. PLoS One. 2017;12(2):e0171127.
- Blumenstock S, Dudanova I. Cortical and striatal circuits in Huntington’s Disease. Front Neurosci. 2020;14:82.
- Yates D. Neurodegenerative disease: revealing cellular targets in HD. Nat Rev Neurosci. 2014 Jun;15(6):350–351.
- Wang N, Gray M, Lu XH, et al. Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington’s disease. Nat Med. 2014 May;20(5):536–541.
- Sashital DG, Doudna JA. Structural insights into RNA interference. Curr Opin Struct Biol. 2010 Feb;20(1):90–97.
- Lam JKW, Chow MYT, Zhang Y, et al. siRNA Versus miRNA as therapeutics for gene silencing. Mol Ther-Nucl Acids. 2015 Sep 15;4:e252.
- Das M, Musetti S, Huang L, et al. Drugs: the roadblocks, and the “Delivery” of the promise. Nucleic Acid Ther. 2019 Apr;29(2):61–66.
- Dyawanapelly S, Ghodke SB, Vishwanathan R, et al. RNA interference-based therapeutics: molecular platforms for infectious diseases. J Biomed Nanotechnol. 2014 Sep;10(9):1998–2037.
- Pereira TC, Lopes-Cendes I. Medical applications of RNA interference (RNAi). BMC Proc. 2013;7(Suppl 2):K21.
- Liu F, Wang C, Gao Y, et al. Current Transport Systems and Clinical Applications for Small Interfering RNA (siRNA) Drugs. Mol Diagn Ther. 2018 Oct;22(5):551–569.
- Voyager Therapeutics Provides Regulatory Update On VY-HTT01 Program [Internet]. 2020; [cited 2020 Oct 12]. Available from: https://ir.voyagertherapeutics.com/news-releases/news-release-details/voyager-therapeutics-provides-regulatory-update-vy-htt01-program
- Huntington’s Disease 2018. [ updated; cited 2018 Sep 21]. Available from: https://sparktx.com/pipelines/huntingtons-disease/
- Novartis receives US Food and Drug Administration (FDA) Orphan Drug Designation for branaplam (LMI070) in Huntington’s disease (HD) [Internet]. 2020; [ updated 2020 Oct 21; cited 2021 Feb 21]. Available from: https://www.novartis.com/news/media-releases/novartis-receives-us-food-and-drug-administration-fda-orphan-drug-designation-branaplam-lmi070-huntington%27s-disease-hd
- Novartis Releases Update on LMI070 (Branaplam) Clinical Trial [Internet]. 2017; [cited 2017 Sep 19]. Available from: https://www.curesma.org/novartis-releases-update-on-lmi070-branaplam-clinical-trial/
- PTC Therapeutics Announces that PTC518 Has Entered into a Phase 1 Clinical Trial for the Huntington’s Disease Program [Internet]. 2020; [cited 2020 Nov 17]. Available from: https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-that-ptc518-has-entered-into-a-phase-1-clinical-trial-for-the-huntingtons-disease-program-301174225.html
- Therapeutics S Skyhawk Therapeutics Announces Strategic Collaboration with Celgene to Discover and Develop Novel mRNA Splicing Modifiers using Skyhawk’s STAR* Technology Platform. 2018 June 26, 2018
- Therapeutics T Approach Triplet Therapeutics [cited 2021 Feb 21]. Available from: https://www.triplettx.com/approach/
- Jones L, Houlden H, Tabrizi SJ. DNA repair in the trinucleotide repeat disorders. Lancet Neurol. 2017 Jan;16(1):88–96.
- Triplet Therapeutics Completes Enrollment of SHIELD HD Natural History Study of Huntington’s Disease [Internet]. 2020; [cited 2020 Nov 12]. Available from: https://www.businesswire.com/news/home/20201112005275/en/Triplet-Therapeutics-Completes-Enrollment-of-SHIELD-HD-Natural-History-Study-of-Huntington%E2%80%99s-Disease
- Triplet Therapeutics Selects Clinical Candidate for Novel Treatment of Repeat Expansion Disorders [Internet]. 2020; [cited 2020 Jul 21]. Available from: https://www.businesswire.com/news/home/20200721005209/en/Triplet-Therapeutics-Selects-Clinical-Candidate-for-Novel-Treatment-of-Repeat-Expansion-Disorders
- Mittelman D, Moye C, Morton J, et al. Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells. Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9607–9612.
- Garriga-Canut M, Agustin-Pavon C, Herrmann F, et al. Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):E3136–45.
- Zeitler B, Froelich S, Marlen K, et al. Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease. Nat Med. 2019 Jul;25(7):1131–1142.
- Fink KD, Deng P, Gutierrez J, et al. Allele-Specific reduction of the mutant huntingtin allele using transcription activator-like effectors in human Huntington’s disease fibroblasts. Cell Transplant. 2016;25(4):677–686.
- Dabrowska M, Juzwa W, Krzyzosiak WJ, et al. Precise excision of the CAG tract from the huntingtin gene by Cas9 nickases. Front Neurosci. 2018;12:75.
- Yang S, Chang R, Yang H, et al. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. J Clin Invest. 2017 Jun 30;127(7):2719–2724.
- Pattanayak V, Ramirez CL, Joung JK, et al. Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection. Nat Methods. 2011 Aug 7;8(9):765–770.
- Gabriel R, Lombardo A, Arens A, et al. An unbiased genome-wide analysis of zinc-finger nuclease specificity. Nat Biotechnol. 2011 Aug 7;29(9):816–823.
- Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013 Jan;14(1):49–55.
- Kleinstiver BP, Pattanayak V, Prew MS, et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016 Jan 28;529(7587):490-+.
- Alanis-Lobato G, Zohren J, McCarthy A, et al. Frequent loss of heterozygosity in CRISPR-Cas9-edited early human embryos. Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):e2004832117.
- Zuccaro MV, Xu J, Mitchell C, et al. Allele-Specific chromosome removal after Cas9 cleavage in human embryos. Cell. 2020 Dec 10;183(6):1650–1664 e15.
- Rizzuto R, Duchen MR, Pozzan T. Flirting in little space: the ER/mitochondria Ca2+ liaison. Sci STKE. 2004 Jan 13;2004(215):re1.
- Hayashi T, Su TP. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell. 2007 Nov 2;131(3):596–610.
- Tang TS, Slow E, Lupu V, et al. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington’s disease. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2602–2607.
- Tang TS, Tu H, Chan EY, et al. Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron. 2003 Jul 17;39(2):227–239.
- Gerfen CR, Engber TM, Mahan LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990 Dec 7;250(4986):1429–1432.
- Deng YP, Albin RL, Penney JB, et al. Differential loss of striatal projection systems in Huntington’s disease: a quantitative immunohistochemical study. J Chem Neuroanat. 2004 Jun;27(3):143–164.
- Hodges A, Strand AD, Aragaki AK, et al. Regional and cellular gene expression changes in human Huntington’s disease brain. Hum Mol Genet. 2006 Mar 15;15(6):965–977.
- Southwell AL, Franciosi S, Villanueva EB, et al. Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease. Neurobiol Dis. 2015;76:46–56.
- LaGanke C, Samkoff L, Edwards K, et al. Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial. Neurol Neuroimmunol Neuroinflamm. 2017 Jul;4(4):e367.
- Stout JC, Queller S, Baker KN, et al. HD-CAB: a cognitive assessment battery for clinical trials in Huntington’s disease 1,2,3. Mov Disord. 2014 Sep;29(10):1281–1288.
- Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007 Jul;4(7):28–37.
- Vaccinex, Inc. Announces preliminary data from the SIGNAL clinical trial (Investigational Drug VX15/2503 as a potential treatment for Huntington’s Disease) [Internet]. 2017; [ updated April 24, 2017; cited 2021 Feb 28]. Available from: http://www.globenewswire.com/news-release/2017/04/24/970347/0/en/Vaccinex-Inc-Announces-Preliminary-Data-from-the-SIGNAL-Clinical-Trial-Investigational-Drug-VX15-2503-as-a-Potential-Treatment-for-Huntington-s-Disease.html
- Evans E, editor Results of Phase 2 Huntington’s Disease Trial of Anti-Semaphorin 4D Antibody Pepinemab (SIGNAL) Will Guide Clinical Trial in Alzheimer’s Disease. AD/PD 2021; [cited 2021 Mar 9]. Virtual.
- Prilenia Enrolls First Patients into its PROOF-HD Phase 3 Clinical Trial for Huntington’s Disease in the United States [Internet]. 2020; [cited 2020 Oct 27]. Available from: https://www.prilenia.com/first-proof-hd-patients
- Grachev ID, Meyer PM, Becker GA, et al. Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [(18)F] fluspidine and [(18)F] fallypride PET study. Eur J Nucl Med Mol Imaging. 2021 Aug;48(4):1103-1115. DOI: https://doi.org/10.1007/s00259-020-05030-3.
- Huntington Study Group HI. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington’s disease. Mov Disord. 2013 Sep;28(10):1407–1415.
- De Yebenes JG, Landwehrmeyer B, Squitieri F, et al. Pridopidine for the treatment of motor function in patients with Huntington’s disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011 Dec;10(12):1049–1057.
- Waters S, Tedroff J, Ponten H, et al. Pridopidine: overview of pharmacology and rationale for its use in Huntington’s Disease. J Huntingtons Dis. 2018;7(1):1–16.
- Reilmann R, McGarry A, Grachev ID, et al. Safety and efficacy of pridopidine in patients with Huntington’s disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study. Lancet Neurol. 2019 Feb;18(2):165–176.
- McGarry A, Leinonen M, Kieburtz K, et al. Effects of pridopidine on functional capacity in early-stage participants from the PRIDE-HD study. Journal of Huntington’s Disease. 2020;9(4):371–380.
- McGarry A, Auinger P, Kieburtz K, et al. Additional safety and exploratory efficacy data at 48 and 60 months from open-HART, an open-label extension study of pridopidine in Huntington Disease. J Huntingtons Dis. 2020;9(2):173–184.