Focused Ultrasound Therapy
Focused ultrasound is a rapidly evolving, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with Alzheimer’s disease. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects without incisions or radiation. One mechanism is the temporary opening of the blood-brain barrier (BBB), which may aid in the removal of beta amyloid or tao from the brain. In addition, potentially promising drug and antibody therapies are often limited by their inability to cross the BBB in high enough concentrations to have an impact in the brain, and opening the BBB may enable these therapeutic agents to access the brain. An additional mechanism is the ability to use neuromodulation to increase the activity of selected targets in patients with Alzheimer’s disease.
Promising preclinical studies have demonstrated the potential of focused ultrasound to enhance the delivery of therapeutic drugs or antibodies to the brain. Focused ultrasound in combination with microbubbles can safely open the BBB and enable enhanced delivery of anti-amyloid antibodies to the brain. Studies suggest that this method can reduce the number of plaques and improve cognition in Alzheimer’s disease models. Furthermore, focused ultrasound and microbubbles alone (no antibodies) have had similar effects in two different Alzheimer’s models.
Potential advantages
- Focused ultrasound is noninvasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection and blood clots.
- Precise targeting minimizes damage to non-targeted healthy brain.
- Treatment can be a complement to drug therapy, enabling enhanced delivery of disease-modifying therapies into the brain via temporary opening of the blood-brain barrier.
Clinical Trials
A clinical trial in West Virginia is combining opening of the BBB with Aducanumab in patients with early cognitive disability or Alzheimer’s disease.
A Phase II trial at Sunnybrook Health Sciences Centre in Toronto, Canada, is investigating the use of focused ultrasound to temporarily open the BBB in multiple regions of the brain.
A clinical trial in the US is opening the BBB with MR-guided focused ultrasound in patients with Alzheimer’s disease.
See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >
Preclinical Laboratory Studies
Preclinical studies suggest focused ultrasound’s potential to reduce amyloid plaques and improve cognition in Alzheimer’s models. Active studies are assessing focused ultrasound-induced BBB opening to improve the delivery of:
- Anti-amyloid antibodies and other disease modifying drugs (Sunnybrook Health Sciences Centre; Columbia University; Queensland University – Australia; Brigham and Women’s Hospital)
- Anti-tau antibodies (Queensland University – Australia).
Additional Information
Alzheimer’s Association
ExAblate Neuro by Insightec LTD
Notable Papers
Suggested Reading: Focused Ultrasound: Transforming treatment of Neurodegenerative Diseases. August 2022
Suggested Reading: Focused Ultrasound for Alzheimer’s Disease. January 2022.
Fernández-Castaño R, Fernández-Blázquez MÁ, Echevarría-Fernández I, Cabrera-Freitag M, Freitag K. Effect of Transcranial Pulse Stimulation for the Treatment of Alzheimer´s Disease and its Related Symptoms. Curr Alzheimer Res. 2023 Jul 27. doi: 10.2174/1567205020666230727102025. PMID: 37497687
Antoniou A, Stavrou M, Evripidou N, Georgiou E, Kousiappa I, Koupparis A, Papacostas SS, Kleopa KA, Damianou C. FUS-mediated blood-brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice. J Ultrasound. 2023 Jul 29. doi: 10.1007/s40477-023-00805-4. PMID: 37516718
Yoo SS, Kim E, Kowsari K, Van Reet J, Kim HC, Yoon K. Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound. Sci Rep. 2023 Jul 31;13(1):12339. doi: 10.1038/s41598-023-39640-2. PMID: 37524783
Rezai AR, Ranjan M, Haut MW, Carpenter J, D’Haese PF, Mehta RI, Najib U, Wang P, Claassen DO, Chazen JL, Krishna V, Deib G, Zibly Z, Hodder SL, Wilhelmsen KC, Finomore V, Konrad PE, Kaplitt M, Kaplitt M. Focused ultrasound-mediated blood-brain barrier opening in Alzheimer’s disease: long-term safety, imaging, and cognitive outcomes. J Neurosurg. 2023 Jul 1;139(1):275-283. doi: 10.3171/2022.9.JNS221565. PMID: 36334289
Mehta RI, Carpenter JS, Mehta RI, Haut MW, Wang P, Ranjan M, Najib U, D’Haese PF, Rezai AR. Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer’s disease. Fluids Barriers CNS. 2023 Jun 16;20(1):46. doi: 10.1186/s12987-023-00447-y. PMID: 37328855
Kuo YY, Chen WT, Lin GB, Chen YM, Liu HH, Chao CY. Thermal cycling-hyperthermia ameliorates Aβ25-35-induced cognitive impairment in C57BL/6 mice. Neurosci Lett. 2023 Jun 12;810:137337. doi: 10.1016/j.neulet.2023.137337. PMID: 37315732
Ye D, Chen S, Liu Y, Weixel C, Hu Z, Yuan J, Chen H. Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles. Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2212933120. doi: 10.1073/pnas.2212933120. Epub 2023 May 15. PMID: 37186852
Kong C, Ahn JW, Kim S, Park JY, Na YC, Chang JW, Chung S, Chang WS. Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer’s disease. Brain Stimul. 2023 May 19;16(3):857-866. doi: 10.1016/j.brs.2023.05.014. PMID: 37211337
Gouveia FV, Lea-Banks H, Aubert I, Lipsman N, Hynynen K, Hamani C. Anesthetic-loaded nanodroplets with focused ultrasound reduces agitation in Alzheimer’s mice. Ann Clin Transl Neurol. 2023 Apr;10(4):507-519. doi: 10.1002/acn3.51737. Epub 2023 Jan 30.
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, Chen H. Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. 2023 Apr;307(2):e220869. doi: 10.1148/radiol.220869. Epub 2023 Jan 31.
Meng Y, Goubran M, Rabin JS, McSweeney M, Ottoy J, Pople CB, Huang Y, Storace A, Ozzoude M, Bethune A, Lam B, Swardfager W, Heyn C, Abrahao A, Davidson B, Hamani C, Aubert I, Zetterberg H, Ashton NJ, Karikari TK, Blennow K, Black SE, Hynynen K, Lipsman N. Blood-brain barrier opening of the default mode network in Alzheimer’s disease with magnetic resonance-guided focused ultrasound. Brain. 2023 Jan 25:awac459. doi: 10.1093/brain/awac459. PMID: 36694943
Gouveia FV, Lea-Banks H, Aubert I, Lipsman N, Hynynen K, Hamani C. Anesthetic-loaded nanodroplets with focused ultrasound reduces agitation in Alzheimer’s mice. Ann Clin Transl Neurol. 2023 Jan 30. doi: 10.1002/acn3.51737. PMID: 36715553
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, Chen H. Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. 2023 Jan 31:220869. doi: 10.1148/radiol.220869.
Kong C, Yang EJ, Shin J, Park J, Kim SH, Park SW, Chang WS, Lee CH, Kim H, Kim HS, Chang JW. Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice, an AD model. Transl Neurodegener. 2022 Dec 27;11(1):57. doi: 10.1186/s40035-022-00333-x.
Choi HJ, Han M, Jung B, Hong YR, Shin S, Lim S, Lee EH, Kim YK, Park J. Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation. Biomedicines. 2022 Dec 8;10(12):3191. doi: 10.3390/biomedicines10123191.
Rezai AR, Ranjan M, Haut MW, Carpenter J, D’Haese PF, Mehta RI, Najib U, Wang P, Claassen DO, Chazen JL, Krishna V, Deib G, Zibly Z, Hodder SL, Wilhelmsen KC, Finomore V, Konrad PE, Kaplitt M, Kaplitt M. Focused ultrasound-mediated blood-brain barrier opening in Alzheimer’s disease: long-term safety, imaging, and cognitive outcomes. J Neurosurg. 2022 Nov 4:1-9. doi: 10.3171/2022.9.JNS221565.
Cheyuo C, Germann J, Yamamoto K, Vetkas A, Loh A, Sarica C, Milano V, Zemmar A, Flouty O, Harmsen IE, Hodaie M, Kalia SK, Tang-Wai D, Lozano AM. Connectomic neuromodulation for Alzheimer’s disease: A systematic review and meta-analysis of invasive and non-invasive techniques. Transl Psychiatry. 2022 Nov 21;12(1):490. doi: 10.1038/s41398-022-02246-9.
Wang J, Li Z, Pan M, Fiaz M, Hao Y, Yan Y, Sun L, Yan F. Ultrasound-mediated blood-brain barrier opening: An effective drug delivery system for theranostics of brain diseases. Adv Drug Deliv Rev. 2022 Nov;190:114539. doi: 10.1016/j.addr.2022.114539. Epub 2022 Sep 15.
Bajracharya R, Cruz E, Götz J, Nisbet RM. Ultrasound-mediated delivery of novel tau-specific monoclonal antibody enhances brain uptake but not therapeutic efficacy. J Control Release. 2022 Sep;349:634-648. doi: 10.1016/j.jconrel.2022.07.026. Epub 2022 Jul 27.
Xhima K, Markham-Coultes K, Hahn Kofoed R, Saragovi HU, Hynynen K, Aubert I. Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies. Brain. 2022 Aug 27;145(8):2806-2822. doi: 10.1093/brain/awab460.
Click here for additional references from PubMed.
