Parkinson's Disease

Last Updated: 22 May 2023

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

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 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.

Please note that for work being done on dementia, including that which is associated with Parkinson’s disease, please see the Disease and Conditions listing for Dementia.

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.

Advantages
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, 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.

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 disease tremor (neuromodulation)
A clinical trial in Los Angeles is using transcranial ultrasound neuromodulation to treat patients with essential tremor.

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 has completed enrollment of patients.

Parkinson’s dyskinesia (unilateral subthalamotomy)
This trial has completed enrollment of patients.

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

Notable Papers

Blesa J, Pineda-Pardo JA, Inoue KI, Gasca-Salas C, Balzano T, Del Rey NL, Reinares-Sebastián A, Esteban-García N, Rodríguez-Rojas R, Márquez R, Ciorraga M, Del Álamo M, García-Cañamaque L, Ruiz de Aguiar S, Rachmilevitch I, Trigo-Damas I, Takada M, Obeso JA. BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging. Sci Adv. 2023 Apr 21;9(16):eadf4888. doi: 10.1126/sciadv.adf4888. Epub 2023 Apr 19.

Martínez-Fernández R, Natera-Villalba E, Máñez Miró JU, Rodriguez-Rojas R, Marta Del Álamo M, Pineda-Pardo JÁ, Ammann C, Obeso I, Mata-Marín D, Hernández-Fernández F, Gasca-Salas C, Matarazzo M, Alonso-Frech F, Obeso JA. Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease. Neurology. 2023 Mar 28;100(13):e1395-e1405. doi: 10.1212/WNL.0000000000206771. Epub 2023 Jan 11.

Kiani L. Ultrasound ablation treatment for PD. Nat Rev Neurol. 2023 Apr;19(4):197. doi: 10.1038/s41582-023-00797-z.

Lu H, Wang X, Lou X. Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson’s disease. Chin Med J (Engl). 2023 Mar 14. doi: 10.1097/CM9.0000000000002319.

Yamaguchi T, Nakano M, Sasanuma J, Takasaki M, Maki F, Hino S, Kaburagi M, Iijima K, Iwamuro H, Watanabe K. Cavitation with low-energy sonication during focused ultrasound thalamotomy for a patient with tremor-dominant Parkinson’s disease: a potential risk. Acta Neurochir (Wien). 2023 Mar 14. doi: 10.1007/s00701-023-05551-4.

Maamary J, Peters J, Kyle K, Barnett Y, Jonker B, Tisch S. Effective Subthalamic Nucleus Deep Brain Stimulation Following MRgFUS for Tremor Dominant Parkinson’s Disease. Mov Disord Clin Pract. 2023 Jan 30;10(3):486-492. doi: 10.1002/mdc3.13662. eCollection 2023 Mar.

He X, Oshino S, Hosomi K, Kanemoto M, Tani N, Kishima H. Characteristics of Pain During MRI-Guided Focused Ultrasound Thalamotomy. Neurosurgery. 2023 Mar 2. doi: 10.1227/neu.0000000000002420.

Pirker W, Katzenschlager R, Hallett M, Poewe W. Pharmacological Treatment of Tremor in Parkinson’s Disease Revisited. J Parkinsons Dis. 2023 Feb 21. doi: 10.3233/JPD-225060.

Krishna V, Fishman PS, Eisenberg HM, Kaplitt M, Baltuch G, Chang JW, Chang WC, Martinez Fernandez R, Del Alamo M, Halpern CH, Ghanouni P, Eleopra R, Cosgrove R, Guridi J, Gwinn R, Khemani P, Lozano AM, McDannold N, Fasano A, Constantinescu M, Schlesinger I, Dalvi A, Elias WJ.Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson’s Disease. N Engl J Med. 2023 Feb 23;388(8):683-693. doi: 10.1056/NEJMoa2202721.

Schrag A. Focused Ultrasound Ablation of the Globus Pallidus Internus for Parkinson’s Disease. N Engl J Med. 2023 Feb 23;388(8):759-760. doi: 10.1056/NEJMe2215506.

Yuen J, Goyal A, Kaufmann TJ, Jackson LM, Miller KJ, Klassen BT, Dhawan N, Lee KH, Lehman VT. Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor. J Neurosurg. 2023 Jan 1;138(1):50-57. doi: 10.3171/2022.5.JNS22350.

Saporito G, Sucapane P, Ornello R, Cerone D, Bruno F, Splendiani A, Masciocchi C, Ricci A, Marini C, Sacco S, Pistoia F. Cognitive outcomes after focused ultrasound thalamotomy for tremor: Results from the COGNIFUS (COGNitive in Focused UltraSound) study. Parkinsonism Relat Disord. 2023 Jan;106:105230. doi: 10.1016/j.parkreldis.2022.105230. Epub 2022 Nov 28.

Moro E, Romito LM. Unilateral Focused Ultrasound Subthalamotomy for Parkinson Disease: Long-term Efficacy and Safety. Neurology. 2023 Jan 11:10.1212/WNL.0000000000206896. doi: 10.1212/WNL.0000000000206896.

Fabbri M, Barbosa R, Rascol O. Off-time Treatment Options for Parkinson’s Disease. Neurol Ther. 2023 Jan 12. doi: 10.1007/s40120-022-00435-8.

Blitz SE, Torre M, Chua MMJ, Christie SL, McDannold NJ, Cosgrove GR. Focused Ultrasound Thalamotomy: Correlation of Postoperative Imaging with Neuropathological Findings. Stereotact Funct Neurosurg. 2023 Jan 25:1-8. doi: 10.1159/000527269.

Chen JC, Lu MK, Chen CM, Tsai CH. Stepwise Dual-target MR-guided Focused Ultrasound in Tremor-dominant Parkinson’s Disease: a Feasibility Study. World Neurosurg. 2022 Dec 20:S1878-8750(22)01753-3. doi: 10.1016/j.wneu.2022.12.049.

Trinh D, Nash J, Goertz D, Hynynen K, Bulner S, Iqbal U, Keenan J. Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of AAV-2 SIRT-3. Drug Deliv. 2022 Dec;29(1):1176-1183. doi: 10.1080/10717544.2022.2035855.

Golfrè Andreasi N, Cilia R, Romito LM, Bonvegna S, Straccia G, Elia AE, Novelli A, Messina G, Tringali G, Levi V, Devigili G, Rinaldo S, Gasparini V, Grisoli M, Stanziano M, Ghielmetti F, Prioni S, Bocchi E, Amami P, Piacentini SHMJ, Ciceri EFM, Bruzzone MG, Eleopra R. Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson’s Disease: A Pilot Study. Mov Disord. 2022 Nov;37(11):2289-2295. doi: 10.1002/mds.29200. Epub 2022 Aug 29.

Feng Y, An R, Zhang Y, Chen M, Wang L, Duan Y, Xing C. AHNAK-modified microbubbles for the intracranial delivery of triptolide: In-vitro and in-vivo investigations. Int J Pharm. 2022 Dec 15;629:122351. doi: 10.1016/j.ijpharm.2022.122351. Epub 2022 Oct 29.

Hvingelby VS, Pavese N. Surgical Advances in Parkinson’s Disease. Curr Neuropharmacol. 2022 Nov 21. doi: 10.2174/1570159X21666221121094343.

Zhang H, Xu M, Zhang Y, Wang X, Zhang C, He F, Song X, Chen S, Jian X, Ming D. Numerical simulation study of firing threshold of STN neuron stimulated by focused ultrasound. IEEE Trans Biomed Eng. 2022 Oct 28;PP. doi: 10.1109/TBME.2022.3217831.

Pineda-Pardo JA, Gasca-Salas C, Fernández-Rodríguez B, Rodríguez-Rojas R, Del Álamo M, Obeso I, Hernández-Fernández F, Trompeta C, Martínez-Fernández R, Matarazzo M, Mata-Marín D, Guida P, Duque A, Albillo D, Plaza de Las Heras I, Montero JI, Foffani G, Toltsis G, Rachmilevitch I, Blesa J, Obeso JA. Striatal Blood-Brain Barrier Opening in Parkinson’s Disease Dementia: A Pilot Exploratory Study. Mov Disord. 2022 Oct;37(10):2057-2065. doi: 10.1002/mds.29134. Epub 2022 Jun 28.

Kim E, Van Reet J, Kim HC, Kowsari K, Yoo SS. High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection. Pharmaceutics. 2022 Oct 6;14(10):2120. doi: 10.3390/pharmaceutics14102120.

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society – European Section guideline on the treatment of Parkinson’s disease: I. Invasive therapies. Eur J Neurol. 2022 Sep;29(9):2580-2595. doi: 10.1111/ene.15386. Epub 2022 Jul 6.

Meng Y, Pople CB, Huang Y, Jones RM, Ottoy J, Goubran M, Oliveira LM, Davidson B, Lawrence LSP, Lau AZ, Bethune A, Maralani P, Abrahao A, Hamani C, Hynynen K, Kalia SK, Lipsman N, Kalia LV. Putaminal Recombinant Glucocerebrosidase Delivery with Magnetic Resonance-Guided Focused Ultrasound in Parkinson’s Disease: A Phase I Study. Mov Disord. 2022 Sep 11. doi: 10.1002/mds.29190.

Golfrè Andreasi N, Cilia R, Romito LM, Bonvegna S, Straccia G, Elia AE, Novelli A, Messina G, Tringali G, Levi V, Devigili G, Rinaldo S, Gasparini V, Grisoli M, Stanziano M, Ghielmetti F, Prioni S, Bocchi E, Amami P, Piacentini SHMJ, Ciceri EFM, Bruzzone MG, Eleopra R. Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson’s Disease: A Pilot Study. Mov Disord. 2022 Aug 29. doi: 10.1002/mds.29200.

Yin C, Zong R, Song G, Zhou J, Pan L, Li X. Comparison of Motor Scores between OFF and ON States in Tremor-Dominant Parkinson’s Disease after MRgFUS Treatment. J Clin Med. 2022 Aug 2;11(15):4502. doi: 10.3390/jcm11154502. PMID: 35956119

Leung SA, Moore D, Gilbo Y, Snell J, Webb TD, Meyer CH, Miller GW, Ghanouni P, Butts Pauly K. Comparison between MR and CT imaging used to correct for skull-induced phase aberrations during transcranial focused ultrasound. Sci Rep. 2022 Aug 4;12(1):13407. doi: 10.1038/s41598-022-17319-4. PMID: 35927449

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 Jul;56(1):35-44. doi: 10.1002/jmri.28080. Epub 2022 Jan 26. PMID: 35081263

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society-European Section Guideline on the Treatment of Parkinson’s Disease: I. Invasive Therapies. Mov Disord. 2022 Jul;37(7):1360-1374. doi: 10.1002/mds.29066. Epub 2022 Jul 6.

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 Jul;56(1):35-44. doi: 10.1002/jmri.28080. Epub 2022 Jan 26.

Lin SJ, Rodriguez-Rojas R, Baumeister TR, Lenglos C, Pineda-Pardo JA, Máñez-Miró JU, Del Alamo M, Martinez-Fernandez R, Obeso JA, Iturria-Medina Y. Neuroimaging signatures predicting motor improvement to focused ultrasound subthalamotomy in Parkinson’s disease. NPJ Parkinsons Dis. 2022 Jun 3;8(1):70. doi: 10.1038/s41531-022-00332-9.

Pineda-Pardo JA, Gasca-Salas C, Fernández-Rodríguez B, Rodríguez-Rojas R, Del Álamo M, Obeso I, Hernández-Fernández F, Trompeta C, Martínez-Fernández R, Matarazzo M, Mata-Marín D, Guida P, Duque A, Albillo D, Plaza de Las Heras I, Montero JI, Foffani G, Toltsis G, Rachmilevitch I, Blesa J, Obeso JA. Striatal Blood-Brain Barrier Opening in Parkinson’s Disease Dementia: A Pilot Exploratory Study. Mov Disord. 2022 Jun 28. doi: 10.1002/mds.29134.

Stieglitz LH, Mahendran S, Oertel MF, Baumann CR. Bilateral Focused Ultrasound Pallidotomy for Parkinson-Related Facial Dyskinesia-A Case Report. Mov Disord Clin Pract. 2022 May 9;9(5):647-651. doi: 10.1002/mdc3.13462. eCollection 2022 Jul.

Koga S, Ishaque M, Jeffrey Elias W, Shah BB, Murakami A, Dickson DW. Neuropathology of Parkinson’s disease after focused ultrasound thalamotomy. NPJ Parkinsons Dis. 2022 May 12;8(1):59. doi: 10.1038/s41531-022-00319-6.

Menon S, Armstrong S, Hamzeh A, Visanji NP, Sardi SP, Tandon A. Alpha-Synuclein Targeting Therapeutics for Parkinson’s Disease and Related Synucleinopathies. Front Neurol. 2022 May 9;13:852003. doi: 10.3389/fneur.2022.852003. eCollection 2022.

Páez-Nova M, Spiegelmann R, Korn-Israeli S, Zibly Z, Illera-Rivera D, Daza-Cordoba C, Alcazar-Daza JC, Garcia-Ballestas E. Targeting the vim by direct visualization of the cerebello-thalamo-cortical pathway in 3 T proton density MRI: correlation with focused ultr a sound lesioning. Neurosurg Rev. 2022 Jun;45(3):2323-2332. doi: 10.1007/s10143-022-01752-0. Epub 2022 Feb 11.

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.

Click here for additional references on PubMed.

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