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Review Article
Gene Therapy for Huntington’s Disease: The Final Strategy for a Cure?
Seulgi Byun, Mijung Lee, Manho Kim
J Mov Disord. 2022;15(1):15-20.   Published online November 17, 2021
  • 7,519 View
  • 437 Download
  • 13 Web of Science
  • 11 Crossref
AbstractAbstract PDF
Huntington’s disease (HD) has become a target of the first clinical trials for gene therapy among movement disorders with a genetic origin. More than 100 clinical trials regarding HD have been tried, but all failed, although there were some improvements limited to symptomatic support. Compared to other neurogenetic disorders, HD is known to have a single genetic target. Thus, this is an advantage and its cure is more feasible than any other movement disorder with heterogeneous genetic causes. In this review paper, the authors attempt to cover the characteristics of HD itself while providing an overview of the gene transfer methods currently being researched, and will introduce an experimental trial with a preclinical model of HD followed by an update on the ongoing clinical trials for patients with HD.


Citations to this article as recorded by  
  • The Huntington's Disease Gene Discovery
    Gustavo L. Franklin, Hélio A.G. Teive, Fernando Spina Tensini, Carlos Henrique Ferreira Camargo, Nayra de Souza Carvalho de Lima, Diego de Castro de dos Santos, Alex T. Meira, Sarah J. Tabrizi
    Movement Disorders.2024; 39(2): 227.     CrossRef
  • Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models
    Matthew J. Barrett, Ahmed Negida, Nitai Mukhopadhyay, Jin K. Kim, Huma Nawaz, Jefin Jose, Claudia Testa
    Movement Disorders.2024; 39(5): 855.     CrossRef
  • Exosomes for neurodegenerative diseases: diagnosis and targeted therapy
    Hui Tao, Bo Gao
    Journal of Neurology.2024; 271(6): 3050.     CrossRef
  • Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington’s disease
    Alaa Shafie, Amal Adnan Ashour, Saleha Anwar, Farah Anjum, Md. Imtaiyaz Hassan
    Archives of Pharmacal Research.2024;[Epub]     CrossRef
  • Positron Emission Tomography Quantitative Assessment of Off-Target Whole-Body Biodistribution of I-124-Labeled Adeno-Associated Virus Capsids Administered to Cerebral Spinal Fluid
    Jonathan B. Rosenberg, Edward K. Fung, Jonathan P. Dyke, Bishnu P. De, Howard Lou, James M. Kelly, Layla Reejhsinghani, Rodolfo J. Ricart Arbona, Dolan Sondhi, Stephen M. Kaminsky, Nathalie Cartier, Christian Hinderer, Juliette Hordeaux, James M. Wilson,
    Human Gene Therapy.2023;[Epub]     CrossRef
  • CRISPR: a tool with potential for genomic reprogramming in neurological disorders
    Yogesh K. Dhuriya, Aijaz A. Naik
    Molecular Biology Reports.2023; 50(2): 1845.     CrossRef
  • Gene therapy for selected neuromuscular and trinucleotide repeat disorders – An insight to subsume South Asia for multicenter clinical trials
    Nalaka Wijekoon, Lakmal Gonawala, Pyara Ratnayake, Darshana Sirisena, Harsha Gunasekara, Athula Dissanayake, Sunethra Senanayake, Ajantha Keshavaraj, Yetrib Hathout, Harry W.M. Steinbusch, Chandra Mohan, Ashwin Dalal, Eric Hoffman, K.Ranil D de Silva
    IBRO Neuroscience Reports.2023; 14: 146.     CrossRef
  • Huntington’s Disease Drug Development: A Phase 3 Pipeline Analysis
    Hannah J. Van de Roovaart, Nguyen Nguyen, Timothy D. Veenstra
    Pharmaceuticals.2023; 16(11): 1513.     CrossRef
  • Bioinspired Approaches for Central Nervous System Targeted Gene Delivery
    Jyotish Kumar, Afroz Karim, Ummy Habiba Sweety, Hemen Sarma, Md Nurunnabi, Mahesh Narayan
    ACS Applied Bio Materials.2023;[Epub]     CrossRef
  • Mitochondrial organization and structure are compromised in fibroblasts from patients with Huntington’s disease
    Marie Vanisova, Hana Stufkova, Michaela Kohoutova, Tereza Rakosnikova, Jana Krizova, Jiri Klempir, Irena Rysankova, Jan Roth, Jiri Zeman, Hana Hansikova
    Ultrastructural Pathology.2022; 46(5): 462.     CrossRef
  • Pathogenesis of Huntington’s Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies
    Zainab Irfan, Sofia Khanam, Varnita Karmakar, Sayeed Mohammed Firdous, Bothaina Samih Ismail Abou El Khier, Ilyas Khan, Muneeb U. Rehman, Andleeb Khan
    Brain Sciences.2022; 12(10): 1389.     CrossRef
Original Article
Exosome-Based Delivery of miR-124 in a Huntington’s Disease Model
Soon-Tae Lee, Wooseok Im, Jae-Jun Ban, Mijung Lee, Keun-Hwa Jung, Sang Kun Lee, Kon Chu, Manho Kim
J Mov Disord. 2017;10(1):45-52.   Published online January 18, 2017
  • 16,703 View
  • 369 Download
  • 110 Web of Science
  • 94 Crossref
AbstractAbstract PDF
Huntington’s disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect.
We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells.
When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement.
This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.


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