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Recent preclinical evidence demonstrates that following application of focused ultrasound with microbubbles (FUS+MB), the BBB becomes reversibly accessible to compounds that normally are brain-impermeable, suggesting FUS+MB as a promising new platform for delivery of therapeutic agents into the central nervous system. As a step towards translation, small cohort clinical studies were performed demonstrating safe BBB opening in Alzheimer\u2019s disease, Parkinson\u2019s disease and amyotrophic lateral sclerosis (ALS) patients following FUS+MB, however improved drug delivery has not yet been achieved in human. Simultaneously, rapid progress in the human induced pluripotent stem cell (hiPSC) modeling technology allowed for development of novel Alzheimer\u2019s disease patient-derived BBB\n                    <jats:italic>in vitro<\/jats:italic>\n                    model that reacts to FUS+MB with BBB opening and can be used to answer fundamental questions of human BBB responses to FUS+MB in health and disease. This review summarizes key features of the BBB that contribute to limited drug delivery, recapitulates recent advances in the FUS+MB mediated human BBB opening\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    in the context of neurodegenerative disorders, and highlights potential strategies for fast-track translation of the FUS+MB to improve bioavailability of drugs to the human brain. With safe and effective application, this innovative FUS+MB technology may open new avenues for therapeutic interventions in neurodegenerative diseases leading to improved clinical outcomes for patients.\n                  <\/jats:p>","DOI":"10.1007\/s11095-022-03185-2","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T13:02:47Z","timestamp":1646658167000},"page":"427-439","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["\u201cFocused Ultrasound-mediated Drug Delivery in Humans \u2013 a Path Towards Translation in Neurodegenerative Diseases\u201d"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2423-7868","authenticated-orcid":false,"given":"Joanna M.","family":"Wasielewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-9891","authenticated-orcid":false,"given":"Anthony R.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"1","key":"3185_CR1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1152\/physrev.00050.2017","volume":"99","author":"MD Sweeney","year":"2019","unstructured":"Sweeney MD, Zhao Z, Montagne A, Nelson A, Zlokovic B. 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