FDA Approved square

FDA approved for both Tremor Dominant Parkinson’s Disease and Dyskinesia

Focused Ultrasound Therapy

Focused ultrasound is an early-stage, noninvasive, 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 depart from the brain.

Outside Approval SquareAdvantages
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.

Clinical Trials SquareFocused 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, akinesia or dyskinesia – 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. 

Advantages

  • 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 >

Clinical Trials

There are several recent trials that assess the feasibility, safety, and preliminary efficacy of focused ultrasound to treat different symptoms of Parkinson’s. 

Parkinson’s dyskinesia (unilateral pallidotomy)
This international pivotal trial has completed enrollment of patients. 

Parkinson’s disease (Staged unilateral or bilateral pallidothalamic tractotomy [PTT])
This trial is currently recruiting patients at multiple locations. Please note that patients who have had focused ultrasound treatments for tremor (at the VIM nucleus) or dyskinesia (at the GPi) are not eligible to have the other side treated in this clinical trial. The staged bilateral treatment for this clinical trial is only for patients who had the PTT on the first side.

Parkinson’s dyskinesia (unilateral subthalamotomy)
This trial is recruiting patients with early Parkinson’s disease in Madrid, Spain.

Parkinson’s dyskinesia (unilateral subthalamotomy)
This trial is recruiting patients with movement disorders in Osaka, Japan.

See a list of treatment sites >
See here for a list of clinical trials sites >
See here for a list of laboratory research sites >

Regulatory Approval & Reimbursement

The Exablate system manufactured by Insightec is approved in Europe and in the US for treating tremor-dominant Parkinson's disease. In November 2021, it also earned approval in the US for treating additional movement disorders associated with Parkinson's disease, including mobility, rigidity and dyskinesia. We recommend that patients 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)

Additional Resources

The Michael J. Fox Foundation for Parkinson’s Research
Exablate Neuro by Insightec LTD

Suggested Reading

Parkinson's Disease: Latest Treatments and Research. September 2020. 

Focused Ultrasound for Parkinson's Disease. April 2020. 
(See an archived version from March 2019.)

Notable Papers

Wasielewska JM, White AR. Focused Ultrasound-mediated Drug Delivery in Humans - a Path Towards Translation in Neurodegenerative Diseases. Pharm Res. 2022 Mar;39(3):427-439. doi: 10.1007/s11095-022-03185-2. Epub 2022 Mar 7.

Xiong Y, Han D, He J, Zong R, Bian X, Duan C, Zhang D, Zhou X, Pan L, Lou X. Correlation of visual area with tremor improvement after MRgFUS thalamotomy in Parkinson's disease. J Neurosurg. 2021 Sep 3;136(3):681-688. doi: 10.3171/2021.3.JNS204329. Print 2022 Mar 1.

Yuan J, Liu H, Zhang H, Wang T, Zheng Q, Li Z. Controlled Activation of TRPV1 Channels on Microglia to Boost Their Autophagy for Clearance of Alpha-Synuclein and Enhance Therapy of Parkinson's Disease. Adv Mater. 2022 Mar;34(11):e2108435. doi: 10.1002/adma.202108435. Epub 2022 Feb 6.

Lin CY, Huang CY, Chen CM, Liu HL. Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhanced alpha-Synuclein Expression in Mice for Modeling Parkinson's Disease. Pharmaceutics. 2022 Feb 18;14(2):444. doi: 10.3390/pharmaceutics14020444.

Lee KS, Clennell B, Steward TGJ, Gialeli A, Cordero-Llana O, Whitcomb DJ. Focused Ultrasound Stimulation as a Neuromodulatory Tool for Parkinson's Disease: A Scoping Review. Brain Sci. 2022 Feb 19;12(2):289. doi: 10.3390/brainsci12020289.

Stanziano M, Golfrè Andreasi N, Messina G, Rinaldo S, Palermo S, Verri M, Demichelis G, Medina JP, Ghielmetti F, Bonvegna S, Nigri A, Frazzetta G, D'Incerti L, Tringali G, DiMeco F, Eleopra R, Bruzzone MG. Resting State Functional Connectivity Signatures of MRgFUS Vim Thalamotomy in Parkinson's Disease: A Preliminary Study. Front Neurol. 2022 Jan 12;12:786734. doi: 10.3389/fneur.2021.786734. eCollection 2021.

Wang X, Xiong Y, Lin J, Lou X. Target Selection for Magnetic Resonance-Guided Focused Ultrasound in the Treatment of Parkinson's Disease. J Magn Reson Imaging. 2022 Jan 26. doi: 10.1002/jmri.28080.

Yuan J, Liu H, Zhang H, Wang T, Zheng Q, Li Z. Controlled Activation of TRPV1 Channels on Microglia to Boost Their Autophagy for Clearance of Alpha-Synuclein and Enhance Therapy of Parkinson's Disease. Adv Mater. 2022 Jan 13:e2108435. doi: 10.1002/adma.202108435.

Rodriguez-Rojas R, Pineda-Pardo JA, Mañez-Miro J, Sanchez-Turel A, Martinez-Fernandez R, Del Alamo M, DeLong M, Obeso JA. Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease. Mov Disord. 2021 Dec 3. doi: 10.1002/mds.28862.

van Gool R, Tucker-Bartley A, Yang E, Todd N, Guenther F, Goodlett B, Al-Hertani W, Bodamer OA, Upadhyay J. Targeting neurological abnormalities in lysosomal storage diseases. Trends Pharmacol Sci. 2021 Nov 27:S0165-6147(21)00222-4. doi: 10.1016/j.tips.2021.11.005.

Fishman PS, Fischell JM. Focused Ultrasound Mediated Opening of the Blood-Brain Barrier for Neurodegenerative Diseases. Front Neurol. 2021 Nov 4;12:749047. doi: 10.3389/fneur.2021.749047. eCollection 2021.

Yan Y, Chen Y, Liu Z, Cai F, Niu W, Song L, Liang H, Su Z, Yu B, Yan F. Brain Delivery of Curcumin Through Low-Intensity Ultrasound-Induced Blood-Brain Barrier Opening via Lipid-PLGA Nanobubbles. Int J Nanomedicine. 2021 Nov 4;16:7433-7447. doi: 10.2147/IJN.S327737. eCollection 2021.

Sammartino F, Marsh R, Yeh FC, Sondergaard A, Changizi BK, Krishna V. Radiological identification of the globus pallidus motor subregion in Parkinson's disease. J Neurosurg. 2021 Nov 5:1-9. doi: 10.3171/2021.7.JNS21858.

Jackson LM, Kaufmann TJ, Lehman VT, Lee KH, Miller KJ, Hassan A, Klassen BT. Clinical Characteristics of Patients with Gait Instability after MR-Guided Focused Ultrasound Thalamotomy. Tremor Other Hyperkinet Mov (N Y). 2021 Oct 21;11:41. doi: 10.5334/tohm.643. eCollection 2021.

Sinai A, Nassar M, Sprecher E, Constantinescu M, Zaaroor M, Schlesinger I. Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson's Disease: Long-Term Results. J Parkinsons Dis. 2021 Sep 25. doi: 10.3233/JPD-212810.

Parras O, Domínguez P, Tomás-Biosca A, Guridi J. The role of tractography in the localisation of the Vim nucleus of the thalamus and the dentatorubrothalamic tract for the treatment of tremor. Neurologia (Engl Ed). 2021 Sep 23:S2173-5808(21)00142-5. doi: 10.1016/j.nrleng.2019.09.008.

Lin J, Kang X, Xiong Y, Zhang D, Zong R, Yu X, Pan L, Lou X. Convergent structural network and gene signatures for MRgFUS thalamotomy in patients with Parkinson's disease. Neuroimage. 2021 Sep 1:118550. doi: 10.1016/j.neuroimage.2021.118550.

Xiong Y, Han D, He J, Zong R, Bian X, Duan C, Zhang D, Zhou X, Pan L, Lou X. Correlation of visual area with tremor improvement after MRgFUS thalamotomy in Parkinson's disease. J Neurosurg. 2021 Sep 3:1-8. doi: 10.3171/2021.3.JNS204329.

Yamamoto K, Ito H, Fukutake S, Odo T, Kamei T, Yamaguchi T, Taira T. Focused Ultrasound Thalamotomy for Tremor-dominant Parkinson's Disease: A Prospective 1-year Follow-up Study. Neurol Med Chir (Tokyo). 2021 May 8. doi: 10.2176/nmc.oa.2020-0370.

Jamora RDG, Chang WC, Taira T. Transcranial Magnetic Resonance-Guided Focused Ultrasound in X-Linked Dystonia-Parkinsonism. Life (Basel). 2021 Apr 26;11(5):392. doi: 10.3390/life11050392. P

Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, Martínez-Fernández R, Obeso JA. Present and future of subthalamotomy in the management of Parkinson´s disease: a systematic review. Expert Rev Neurother. 2021 May;21(5):533-545. doi: 10.1080/14737175.2021.1911649. Epub 2021 May 6.

Gallay MN, Moser D, Magara AE, Haufler F, Jeanmonod D. Bilateral MR-Guided Focused Ultrasound Pallidothalamic Tractotomy for Parkinson's Disease With 1-Year Follow-Up. Front. Neurol., 09 February 2021

Gasca-Salas C, Fernández-Rodríguez B, Pineda-Pardo JA, Rodríguez-Rojas R, Obeso I, Hernández-Fernández F, Del Álamo M, Mata D, Guida P, Ordás-Bandera C, Montero-Roblas JI, Martínez-Fernández R, Foffani G, Rachmilevitch I, Obeso JA. Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia. Nat Commun. 2021 Feb 3;12(1):779. doi: 10.1038/s41467-021-21022-9.

Lin F, Wu D, Yu J, Weng H, Chen L, Meng F, Chen Y, Ye Q, Cai G. Comparison of efficacy of deep brain stimulation and focused ultrasound in parkinsonian tremor: a systematic review and network meta-analysis. J Neurol Neurosurg Psychiatry. 2021 Jan 18:jnnp-2020-323656. doi: 10.1136/jnnp-2020-323656.

Click here for additional references on PubMed.

Animated treatment video courtesy of Insightec

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