Focused ultrasound opens the blood-brain barrier

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Carmen Gasca-Salas, José Pineda-Pardo and colleagues in Madrid (HM CINAC) with the device maker InSightec; separately a Sunnybrook / University Health Network team in Toronto (Ying Meng, Nir Lipsman and others), funded in part by the Focused Ultrasound Foundation.

What happened

• Madrid, cortex (NCT03608553, Phase 1, sponsor InSightec, started 26 Nov 2018). Five people with Parkinson's disease dementia, recruited October 2018 to May 2019, had two sessions 2–3 weeks apart, aimed at the right parieto-occipito-temporal cortex. The barrier opened (shown by gadolinium dye leaking into brain) in 8 of 10 treatments. The authors reported no side effects linked to the opening, and the barrier closed again. Mild cognitive improvement was seen and amyloid and glucose-metabolism PET did not change (exploratory). Gasca-Salas et al., Nat Commun 2021;12:779.
• Madrid, striatum (same registry record, amended). Seven people with Parkinson's and cognitive impairment had the posterior putamen opened in two sessions 2–4 weeks apart (three had both putamens in the second session). No serious adverse events, no relevant change in motor or cognitive function, a small drop in amyloid PET uptake in the target and no change in dopamine (FDOPA) PET. Pineda-Pardo et al., Mov Disord 2022;37:2057-2065. The registry now lists 20 enrolled, completed August 2022; results beyond these two papers are not covered here.
• Toronto (NCT04370665, InSightec, started 16 Jul 2020, completed Feb 2022). Four people with early Parkinson's had the barrier opened over the putamen (a movement-control region) and received imiglucerase (Cerezyme), an enzyme replacement for GCase, the lysosome enzyme discussed in landmark 40. Three doses, two weeks apart, followed for 3 and 6 months. The Focused Ultrasound Foundation and Toronto press release report no significant adverse events and "very early" hints of biological effect (Movement Disorders, 2022).
• None of the studies was designed to show benefit, and none had a placebo group.
• Next step. A Phase 1/2 at Sunnybrook (NCT05565443, InSightec sponsor, started 30 Nov 2022, 14 planned, recruiting) will deliver recombinant GCase to both putamens; the primary outcome is adverse events, with primary completion estimated December 2027.

Why it moved us toward a cure

Most protein drugs, enzymes and viruses cannot cross the barrier. The engineered virus shells in landmark 111 work in mice but not yet in primates. Ultrasound is a different route: a noninvasive, repeatable, targeted door that has now been used in people with Parkinson's.

Outcome

Open. Safe and feasible in a handful of patients. No efficacy data. The follow-up trial is another small safety study, not a larger one.

Sources

• Gasca-Salas et al., Nat Commun 2021;12:779, DOI 10.1038/s41467-021-21022-9, PMID 33536430 · NCT03608553 (API, 19 Oct 2026)
• Pineda-Pardo et al., Mov Disord 2022;37:2057-2065, DOI 10.1002/mds.29134
• Focused Ultrasound Foundation summary of the Toronto trial, Sept 2022 · University of Toronto news · NCT04370665 · NCT05565443
• Not yet verified: the Toronto paper's DOI, volume and adverse-event detail (read only via press pages; first author per the Foundation is Ying Meng); whether the Madrid trial's 20 enrolled have been published.