Parkinson’s Disease

Outside Approval Square

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. Where the beams converge, the ultrasound produces a variety of therapeutic effects enabling Parkinson’s disease to be treated without surgery.

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).

Clinical Trials Square

For certain patients, focused ultrasound could provide a non-invasive 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

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.

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.

Disadvantages

  • Compared to deep brain stimulation, focused ultrasound is irreversible and cannot be adjusted or optimized after the procedure.
  • Safety and efficacy for repeated treatments has not yet been determined.
  • Safety and efficacy for bilateral treatments has not yet been determined.
  • Long-term effects of the treatment (i.e. 5 years) are not yet known.

Treating Underlying Pathology

Pre-clinical 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

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. See a list of all Parkinson's clinical trials >

fishman webinar graphicTremor-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 subthalamotomy)
This trial is not currently enrolling patients.

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 for treating tremor-dominant Parkinson's disease. The treatment is not reimbursed by medical payers at this time. 

Pre-Clinical Laboratory Studies

Pre-clinical 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)
  • Anti-alpha synuclein antibodies (Columbia University; HM Puerta del Sur in Madrid/Institut Langevin in Paris)

Additional Resources

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

Notable Papers

Mead BP, Kim N, Miller GW, Hodges D, Mastorakos P, Klibanov AL, Mandell JW, Hirsh J, Suk JS, Hanes J, Price RJ. Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model. Nano Lett. 2017 Jun 14;17(6):3533-3542. doi: 10.1021/acs.nanolett.7b00616. Epub 2017 May 18.

Fasano A, Lozano AM, Cubo E. New neurosurgical approaches for tremor and Parkinson's disease. Curr Opin Neurol. 2017 May 13. doi: 10.1097/WCO.0000000000000465.

Schreglmann SR, Krauss JK, Chang JW, Bhatia KP, Kägi G. Functional lesional neurosurgery for tremor-a protocol for a systematic review and meta-analysis. BMJ Open. 2017 May 9;7(5):e015409. doi: 10.1136/bmjopen-2016-015409.

Alshaikh J, Fishman PS. Revisiting bilateral thalamotomy for tremor. Clin Neurol Neurosurg. 2017 Jul;158:103-107. doi: 10.1016/j.clineuro.2017.04.025. Epub 2017 May 1.

Kinfe TM. Stereotactic MR-guided focused ultrasound deep brain lesioning: the resurrection of posteroventral pallidotomy and thalamotomy for Parkinson's disease? Acta Neurochir (Wien). 2017 Jul;159(7):1367-1369. doi: 10.1007/s00701-017-3161-9. Epub 2017 Mar 31.

Zaaroor M, Sinai A, Goldsher D, Eran A, Nassar M, Schlesinger I. Magnetic resonance-guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases. J Neurosurg. 2017 Feb 24:1-9. doi: 10.3171/2016.10.JNS16758.

Krack P, Martinez-Fernandez R, Del Alamo M, Obeso JA. Current applications and limitations of surgical treatments for movement disorders. Mov Disord. 2017 Jan;32(1):36-52. doi: 10.1002/mds.26890. 

Giugno A, Maugeri R, Graziano F, Gagliardo C, Franzini A, Catalano C, Midiri M, Iacopino DG. Restoring Neurological Physiology: The Innovative Role of High-Energy MR-Guided Focused Ultrasound (HIMRgFUS). Preliminary Data from a New Method of Lesioning Surgery. Acta Neurochir Suppl. 2017;124:55-59. doi: 10.1007/978-3-319-39546-3_9.

Guridi J, Marigil M, Becerra V, Parras O. [Neuroprotective subthalamotomy in Parkinson's disease. The role of magnetic resonance-guided focused ultrasound in early surgery]. Neurocirugia (Astur). 2016 May 5. pii: S1130-1473(16)00035-X. doi: 10.1016/j.neucir.2016.02.006. Spanish. 

Fan CH, Ting CY, Lin CY, Chan HL, Chang YC, Chen YY, Liu HL, Yeh CK. Noninvasive, Targeted, and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson's Disease. Sci Rep. 2016 Jan 20;6:19579. doi: 10.1038/srep19579.

Schlesinger I, Eran A, Sinai A, Erikh I, Nassar M, Goldsher D, Zaaroor M. MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease. Parkinsons Dis. 2015;2015:219149. doi: 10.1155/2015/219149. Epub 2015 Sep 2.

Samiotaki G, Acosta C, Wang S, Konofagou EE. Enhanced delivery and bioactivity of the neurturin neurotrophic factor through focused ultrasound-mediated blood--brain barrier opening in vivo. J Cereb Blood Flow Metab. 2015 Mar 31;35(4):611-22. doi: 10.1038/jcbfm.2014.236.

Magara A, Bühler R, Moser D, Kowalski M, Pourtehrani P, Jeanmonod D; First experience with MR-guided focused ultrasound in the treatment of Parkinson's disease. Journal of Therapeutic Ultrasound 2014, 2:11

Click here for additional references on focused ultrasound for Parkinson's.

Animated treatment video courtesy of Insightec

     

Share this page