Focused Ultrasound Therapy
Focused ultrasound is an early-stage, non-invasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with Parkinson’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 a variety of therapeutic effects enabling Parkinson’s disease to be treated without surgery. For movement disorders, the mechanism is ablation (thermal disruption of the tissue) that can be aimed at several different treatment targets. For the preclinical work in treating the underlying cause, the mechanisms can be temporarily disrupting the blood-brain barrier (BBB), which will allow desired therapeutics the ability to enter the brain. Opening the BBB also can enable undesired materials to more easily leave the brain.
Currently, there is no cure for Parkinson’s and the major options for treatment of motor symptoms include drug therapy and invasive surgery (e.g. deep brain stimulation, radiofrequency lesioning).
For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications and lower cost. In the long term, focused ultrasound has the potential to treat the underlying disease pathology and prevent progression and/or restore function.
Relief of Motor Symptoms
The FDA has approved the use of focused ultrasound for treatment of tremor-dominated Parkinson’s disease. See more in the regulation and approval section, below.
Focused ultrasound has the potential to achieve symptomatic relief by making thermal lesions deep in the brain to interrupt circuits involved with tremor and dyskinesia. Symptoms and targets being assessed for treatment using focused ultrasound include:
- Parkinsonian tremor – target in the thalamus (thalamotomy)
- Parkinsonian dyskinesia – target in the globus pallidus (pallidotomy) or subthalamic nucleus
- Parkinsonian tremor or akinesia – target in the pallidothalamic tract
At this time, focused ultrasound is only being assessed to treat one side of the brain, so it will affect tremor or dyskinesia unilaterally. Studies are being organized to assess the possibility of treating patients bilaterally, and one is included below.
- Focused ultrasound is non-invasive – 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.
- Compared to deep brain stimulation, focused ultrasound is a single procedure, and does not require subsequent procedures/visits to replace batteries, repair broken wires, or adjust simulator settings. It also does not involve the collateral damage to healthy tissue or the risk of infections associated with implanting a foreign body.
Treating Underlying Pathology
Preclinical studies suggest focused ultrasound’s potential to restore function in Parkinson’s models. Focused ultrasound can temporarily open the blood-brain barrier (BBB) to improve the delivery of:
- Genes, growth factors, stem cells, other neuroprotective and/or neurorestorative drugs
- Anti-alpha synuclein antibodies
In October 2018, the Foundation had a multi-disciplinary workshop that aimed at using BBB opening in conjunction with potentially curative agents, to decide what research approaches have the most potential. Read the workshop summary >
There are several recent trials that assess the feasibility, safety, and preliminary efficacy of focused ultrasound to treat different symptoms of Parkinson’s. See a list of all Parkinson's clinical trials >
Tremor-dominant Parkinson's (thalamotomy)
This trial has completed enrollment for patients.
Parkinson's dyskinesia (unilateral pallidotomy)
This trial has completed enrollment for patients.
Parkinson’s dyskinesia (unilateral pallidotomy)
This international pivotal trial has completed enrollment of patients.
Parkinson’s disease (Staged bilateral pallidothalamic tractotomy)
This trial is currently recruiting patients in Tokyo.
Regulatory Approval & Reimbursement
The Exablate system manufactured by Insightec is approved in Europe and in the US for treating tremor-dominant Parkinson's disease. Patients should talk with their physician if they are not sure if they have tremor-dominated Parkinson’s disease. We recommend that they talk with the treatment site for questions about insurance coverage under Medicare, as some treatment sites are now being reimbursed by Medicare. Most commercial companies are not currently covering this procedure.
Preclinical Laboratory Studies
Preclinical studies suggest focused ultrasound’s potential to restore function in Parkinson’s models. Active studies are assessing focused ultrasound-induced BBB opening to improve the delivery of:
- Genes, growth factors, stem cells, other neuroprotective and/or neurorestorative drugs (University of Virginia/Johns Hopkins University; University of Maryland; Columbia University; Chang Gung University in Taiwan; University of Toronto)
- Anti-alpha synuclein antibodies (Columbia University; HM Puerta del Sur in Madrid/Institut Langevin in Paris)
Parkinson's Disease: Latest Treatments and Research. September 2020.
Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, Shah BB, Hernández-Fernández F, Pineda-Pardo JA, Monje MHG, Fernández-Rodríguez B, Sperling SA, Mata-Marín D, Guida P, Alonso-Frech F, Obeso I, Gasca-Salas C, Vela-Desojo L, Elias WJ, Obeso JA. Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease. N Engl J Med. 2020 Dec 24;383(26):2501-2513. doi: 10.1056/NEJMoa2016311.
Perlmutter J, Ushe M. Parkinson's Disease - What's the FUS? N Engl J Med. 2020 Dec 24;383(26):2582-2584. doi: 10.1056/NEJMe2031151.
Sharma VD, Patel M, Miocinovic S. Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics. 2020 Oct 28. doi: 10.1007/s13311-020-00939-x.
McDannold NJ, White PJ, Cosgrove GR. MRI-based thermal dosimetry based on single-slice imaging during focused ultrasound thalamotomy. Phys Med Biol. 2020 Sep 11. doi: 10.1088/1361-6560/abb7c4.
Behl T, Kaur I, Kumar A, Mehta V, Zengin G, Arora S. Gene Therapy in the Management of Parkinson's Disease: Potential of GDNF as a Promising Therapeutic Strategy. Curr Gene Ther. 2020 Aug 17. doi: 10.2174/1566523220999200817164051.
Meng Y, Pople CB, Kalia SK, Kalia LV, Davidson B, Bigioni L, Li DZ, Suppiah S, Mithani K, Scantlebury N, Schwartz ML, Hamani C, Lipsman N. Cost-effectiveness analysis of MR-guided focused ultrasound thalamotomy for tremor-dominant Parkinson's disease. J Neurosurg. 2020 Aug 7:1-6. doi: 10.3171/2020.5.JNS20692.
Martínez-Fernández R, Pineda-Pardo JA. Magnetic resonance-guided focused ultrasound for movement disorders: clinical and neuroimaging advances. Martínez-Fernández R, Pineda-Pardo JA. Curr Opin Neurol. 2020 Aug;33(4):488-497. doi: 10.1097/WCO.0000000000000840.
Miller TR, Guo S, Melhem ER, Eisenberg HM, Zhuo J, Kelm N, Dayan M, Gullapalli RP, Gandhi D. Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson's disease. J Neurosurg. 2020 Apr 24:1-8. doi: 10.3171/2020.2.JNS192590.
Wu CY, Huang RY, Liao EC, Lin YC, Ho YJ, Chang CW, Chan HL, Huang YZ, Hsieh TH, Fan CH, Yeh CK. A preliminary study of Parkinson's gene therapy via sono-magnetic sensing gene vector for conquering extra/intracellular barriers in mice. Brain Stimul. 2020 Feb 24;13(3):786-799. doi: 10.1016/j.brs.2020.02.024.
Lee J, Chang WS, Shin J, Seo Y, Kong C, Song BW, Na YC, Kim BS, Chang JW. Non-invasively enhanced intracranial transplantation of mesenchymal stem cells using focused ultrasound mediated by overexpression of cell-adhesion molecules. Stem Cell Res. 2020 Jan 30;43:101726. doi: 10.1016/j.scr.2020.101726.
Gallay MN, Moser D, Rossi F, Magara AE, Strasser M, Bühler R, Kowalski M, Pourtehrani P, Dragalina C, Federau C and Jeanmonod D (2020) MRgFUS Pallidothalamic Tractotomy for Chronic Therapy-Resistant Parkinson’s Disease in 51 Consecutive Patients: Single Center Experience. Front. Surg. 6:76. doi: 10.3389/fsurg.2019.00076
Ji R, Smith M, Niimi Y, Karakatsani ME, Murillo MF, Jackson-Lewis V, Przedborski S, Konofagou EE. Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson's disease mouse model. Sci Rep. 2019 Dec 18;9(1):19402. doi: 10.1038/s41598-019-55294-5.
Xu Y, He Q, Wang M, Gao Y, Liu X, Li D, Xiong B, Wang W. Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: a systematic review. Neurosurg Rev. 2019 Dec 9. doi: 10.1007/s10143-019-01216-y. Review.
Rodriguez-Rojas R, Pineda-Pardo JA, Martinez-Fernandez R, Kogan RV, Sanchez-Catasus CA, Del Alamo M, Hernández F, García-Cañamaque L, Leenders KL, Obeso JA. Functional impact of subthalamotomy by magnetic resonance-guided focused ultrasound in Parkinson's disease: a hybrid PET/MR study of resting-state brain metabolism. Eur J Nucl Med Mol Imaging. 2019 Nov 8. doi: 10.1007/s00259-019-04497-z.
Valentino F, Cosentino G, Maugeri R, Giammalva R, Iacopino GD, Marrale M, Bartolotta TV, Gagliardo C. Is Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound a Repeatable Treatment Option? Case Report of a Retreated Patient With Tremor Combined With Parkinsonism. Oper Neurosurg (Hagerstown). 2019 Oct 10. pii: opz300. doi: 10.1093/ons/opz300.
Fishman P, Lipsman N. Focused ultrasound as an evolving therapy for Parkinson's disease. Mov Disord. 2019 Sep;34(9):1241-1242. doi: 10.1002/mds.27809. No abstract available.
Foffani G, Trigo-Damas I, Pineda-Pardo JA, Blesa J, Rodríguez-Rojas R, Martínez-Fernández R, Obeso JA. Focused ultrasound in Parkinson's disease: A twofold path toward disease modification. Mov Disord. 2019 Aug 14. doi: 10.1002/mds.27805.
Karakatsani ME, Blesa J, Konofagou EE. Blood-brain barrier opening with focused ultrasound in experimental models of Parkinson's disease. Mov Disord. 2019 Jul 30. doi: 10.1002/mds.27804.
Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman PS. The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson's disease. Mov Disord. 2019 Jul 10. doi: 10.1002/mds.27779.
Gallay M, Moser D, Federau C, Jeanmonod D. Radiological and Thermal Dose Correlations in Pallidothalamic Tractotomy With MRgFUS. Front Surg 2019 May 6:28 DOI=10.3389/fsurg.2019.00028
Cacciola A, Milardi D, Bertino S, Basile GA, Calamuneri A, Chillemi G, Rizzo G, Anastasi G, Quartarone A. Structural connectivity-based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders. Mov Disord. 2019 May 11. doi: 10.1002/mds.27712. [Epub ahead of print] PMID: 31077436
Karakatsani ME, Wang S, Samiotaki G, Kugelman T, Olumolade OO, Acosta C, et al. Amelioration of the nigrostriatal pathway facilitated by ultrasound-mediated neurotrophic delivery in early Parkinson’s disease. J Control Release. 2019 Jun 10;303:289-301. doi: 10.1016/j.jconrel.2019.03.030. Epub 2019 Apr 4.
Gallay MN, Moser D, Federau C, Jeanmonod D. Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note. Front Surg. 2019 Jan 24;6:2. doi: 10.3389/fsurg.2019.00002. eCollection 2019.
Del Rey NL, Quiroga-Varela A, Garbayo E, Carballo-Carbajal I, Fernández-Santiago R, Monje MHG, Trigo-Damas I, Blanco-Prieto MJ, Blesa J. Advances in Parkinson's Disease: 200 Years Later. Front Neuroanat. 2018 Dec 14;12:113. doi: 10.3389/fnana.2018.00113. eCollection 2018.
Zhang H, Sierra C, Kwon N, Karakatsani ME, Jackson-Lewis VR, Przedborski S, et al. Focused-ultrasound Mediated Anti-Alpha-Synuclein Antibody Delivery for the Treatment of Parkinson’s Disease. In: IEEE International Ultrasonics Symposium, IUS. 2018.
Xhima K, Nabbouh F, Hynynen K, Aubert I, Tandon A. Non-invasive delivery of an α-synuclein gene silencing vector with MR-guided focused ultrasound. Movement Disorders 2018 Sept 33:1567-1579. doi: 10.1002/mds.101.
Luk KC. Focal ultrasound strikes a new tune for targeted drug delivery. Movement Disorders 2018 Sept 33:1513-1514. doi: 10.1002/mds.27494.
Ito H, Fukutake S, Yamamoto K, Tanaka S, Yamaguchi T, Taira T, Kamei T. Magnetic Resonance Imaging-guided Focused UltrasoundThalamotomy for Parkinson's Disease with Cardiac Pacemaker: A Case Report. Mov Disord Clin Pract. 2018 Mar 7;5(3):339-340. doi: 10.1002/mdc3.12578. eCollection 2018 May-Jun.
Fasano A, De Vloo P, Llinas M, Hlasny E, Kucharczyk W, Hamani C, Lozano AM. Magnetic resonance imaging-guided focused ultrasound thalamotomy in Parkinson tremor: Reoperation after benefit decay. Mov Disord. 2018 Mar 23. doi: 10.1002/mds.27348.
Antonini A, Moro E, Godeiro C, Reichmann H. Medical and surgical management of advanced Parkinson's disease. Mov Disord. 2018 Mar 23. doi: 10.1002/mds.27340.
Meng Y, Voisin MR, Suppiah S, Kalia SK, Kalia LV, Hamani C, Lipsman N. Is there a role for MR-guided focused ultrasound in Parkinson's disease? Mov Disord. 2018 Apr;33(4):575-579. doi: 10.1002/mds.27308. Epub 2018 Feb 24.
Bretsztajn L, Gedroyc W. Brain-focussed ultrasound: what's the "FUS" all about? A review of current and emerging neurological applications. Br J Radiol. 2018 Mar 6:20170481. doi: 10.1259/bjr.20170481.
Martínez-Fernández R, Rodríguez-Rojas R, Del Álamo M, Hernández-Fernández F, Pineda-Pardo JA, Dileone M, Alonso-Frech F, Foffani G, Obeso I, Gasca-Salas C, de Luis-Pastor E, Vela L, Obeso JA. Focused ultrasound subthalamotomy in patients with asymmetric Parkinson’s disease: a pilot study. Lancet Neurol. 2018 Jan;17(1):54-63. doi: 10.1016/S1474-4422(17)30403-9.
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