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Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have the potential to directly target the disease pathology, such as gene silencing or clearing the mutant protein. However, these agents are limited by their inability to cross the blood-brain barrier (BBB), preventing optimal therapeutic effects. Although various techniques have been explored to overcome the BBB, focused ultrasound (FUS) has emerged as a promising non-invasive therapeutic modality offering the potential for targeted intervention in neurodegenerative diseases, including HD. Preclinical studies demonstrated the safety and efficacy of FUS in delivering therapeutic agents, such as siRNAs and AAV vector-based gene therapy, resulting in significant reductions in mutant HTT expression and improvements in motor function in HD mouse models. Furthermore, the safety profile of FUS-induced BBB opening has been established in clinical trials on human patients of neurodegenerative diseases other than HD, showing no adverse effects on brain structure or function. This review provides a comprehensive overview of the current state of FUS research in HD and connects existing evidence from neurodegenerative disease studies with its promise in establishing disease-modifying therapies for HD.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s11064-024-04302-w","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T05:26:47Z","timestamp":1735882007000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Breaking Barriers in Huntington\u2019s Disease Therapy: Focused Ultrasound for Targeted Drug Delivery"],"prefix":"10.1007","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6387-623X","authenticated-orcid":false,"given":"Mohamed Mohsen","family":"Helal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwa Amer","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Beddor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-0017","authenticated-orcid":false,"given":"Muataz","family":"Kashbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"4302_CR1","unstructured":"Scientific Image and Illustration Software| BioRender"},{"key":"4302_CR2","unstructured":"Huntington\u2019s Disease - Symptoms, Causes, Treatment| NORD"},{"key":"4302_CR3","doi-asserted-by":"crossref","unstructured":"Rojas NG, Cesarini ME, Peker G, Da Prat GA, Etcheverry JL, Gatto EM (2022) Review of Huntington\u2019s Disease: from basics to advances in diagnosis and treatment. 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