MR-Guided Focused Ultrasound + GCase for Parkinson's Disease

Overseen By Nadir Alikacem

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must be taking: PD medications

Must not be taking: Bevacizumab

Disqualifiers: Pregnancy, Diabetes, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Parkinson's disease using a combination of focused ultrasound and GCase, a protein believed to support brain health. The researchers aim to determine if delivering GCase directly to the brain is safe and can improve Parkinson’s symptoms. The trial includes two groups: one for individuals with a specific gene mutation linked to Parkinson's and another for those without this mutation. Individuals who have had Parkinson's for at least two years and are on stable medication might be suitable candidates for this study. As an unphased study, this trial provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Do I need to stop my current medications for this trial?

The trial requires that you have been on a stable regimen of Parkinson's disease medications for at least 90 days before the study, so you should not stop taking your current medications.

What prior data suggests that this technique is safe for Parkinson's Disease patients?

Research has shown that MR-guided Focused Ultrasound (MRgFUS) is generally safe for treating symptoms of Parkinson's disease. Studies have found it effective for patients with tremors unresponsive to medication. Most side effects are mild and temporary, such as headaches or slight discomfort at the treatment site.

Researchers are studying the use of an enzyme called GCase with MRgFUS for potential benefits in Parkinson's disease. While specific safety details for GCase in this context aren't fully available, the focus remains on ensuring its safety for people. Participants in the trial will undergo three treatment cycles, with the option to include GCase after safety checks.

Overall, MRgFUS has a good safety record, with past research suggesting it is well-tolerated. The trial aims to confirm the safety of using both MRgFUS and GCase together for patients with Parkinson's disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about MR-guided Focused Ultrasound Plus GCase for Parkinson's Disease because it offers a unique approach compared to standard treatments like levodopa or dopamine agonists. This treatment uses MR-guided focused ultrasound to temporarily open the blood-brain barrier, allowing for the delivery of GCase, an enzyme that may help address underlying issues in certain Parkinson's patients. This method not only targets the disease more directly but also has the potential to improve symptoms in a way current medications, which primarily manage symptoms, do not. By opening the blood-brain barrier, this treatment could potentially pave the way for more effective delivery of therapeutic agents specifically to the brain.

What evidence suggests that MR-guided Focused Ultrasound Plus GCase is effective for Parkinson's Disease?

Research shows that MR-guided focused ultrasound (MRgFUS) is a promising treatment for Parkinson's disease. Studies have found that MRgFUS can precisely target brain areas linked to movement problems, potentially reducing symptoms. Although more long-term research is needed, early results are encouraging. In this trial, some participants will receive MRgFUS alone, while others may receive MRgFUS with GCase, an enzyme, to enhance results by addressing the root cause of the disease. Animal studies have suggested that GCase can improve Parkinson's symptoms, offering hope for future treatments in humans. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for men and women aged 35-75 with Parkinson's Disease diagnosed at least 2 years ago, at stages 1-3 on medication. Participants must have a positive DAT SPECT scan, be on stable PD meds for over 90 days, and either carry a GBA mutation or not, depending on the study arm. Exclusions include pregnancy, severe kidney issues, other clinical trials participation, hypersensitivity to certain agents used in the study or MRI contrasts.

Inclusion Criteria

Dopaminergic deficit by a positive DAT SPECT scan

Able and willing to give informed consent

American Society of Anesthesiologists (ASA) score 1-3

Exclusion Criteria

My kidney function is severely impaired or I am on dialysis.

Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study

I have had brain surgery for Parkinson's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants receive three transcranial bilateral putamenal GCase treatments at 30 IU/kg IV every two weeks, followed by 60 IU/kg in the next three subjects

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Blood Brain Barrier Disruption - Functional
• MR-guided Focused Ultrasound Plus GCase

Trial Overview

The trial tests if it's safe and doable to deliver GCase directly into the brain using MR-guided Focused Ultrasound (MRgFUS). This method has shown promise in animal studies for improving Parkinson’s symptoms by exposing part of the brain called putamen to GCase.

How Is the Trial Designed?

Group I: Idiopathic PD Patients Experimental Treatment 1 Intervention

Idiopathic PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).

Group II: GBA PD Patients Experimental Treatment 1 Intervention

GBA PD patients receiving 3 cycles of BBBO. There is option to include simultaneous GCase delivery after safety profile review by Data and Safety Monitoring Board (DSMB).

MR-guided Focused Ultrasound Plus GCase is already approved in United States, European Union, Canada for the following indications:

Approved in United States as MRgFUS for:

• Essential Tremor
• Parkinson's disease-related tremor

Approved in European Union as MRgFUS for:

• Essential Tremor
• Parkinson's disease-related tremor

Approved in Canada as MRgFUS for:

• Essential Tremor
• Parkinson's disease-related tremor

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Published Research Related to This Trial

Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless surgical treatment for Parkinson's disease that targets specific areas to alleviate motor symptoms, offering a new option compared to traditional methods like deep brain stimulation (DBS).

While MRgFUS shows promise, it has limitations and potential adverse effects, highlighting the need for careful consideration by neurologists when selecting treatments for patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided focused ultrasound surgery for Parkinson's disease: A mini-review and comparison between deep brain stimulation. Ko, TH., Lee, YH., Chan, L., et al.[2023]

Magnetic resonance guided focused ultrasound (MRgFUS) has been FDA approved for treating essential tremor that doesn't respond to other treatments, highlighting its safety and efficacy as a new intervention.

The article discusses optimization strategies for imaging before, during, and after the procedure, emphasizing the importance of effective MRI techniques to ensure successful ablation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial MR-guided Focused Ultrasound for Essential Tremor : Technical Considerations and Image Guidance. Levi Chazen, J., Stradford, T., Kaplitt, MG.[2020]

In a study of 180 treatments using incisionless magnetic resonance-guided focused ultrasound (MRgFUS) for chronic therapy-resistant conditions like Parkinson's disease and essential tremor, the procedure demonstrated high targeting accuracy with a mean 3D accuracy of 0.73 mm and a low side-effect profile, with only 14 documented side effects (7.8% of treatments).

The procedure resulted in slight cognitive improvements measured by the Montreal Cognitive Assessment (MoCA) at 2 days and 1 year post-treatment, indicating potential benefits for cognitive function without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. Gallay, MN., Moser, D., Jeanmonod, D.[2023]

MRI-guided focused ultrasound is being investigated as a treatment for Parkinson's disease (PD) patients who do not respond to medication, aiming to alleviate their symptoms through targeted brain lesioning.

The review focuses on the clinical outcomes of PD patients treated with this technology, highlighting its potential as a novel intervention for managing difficult-to-treat symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-Guided Focused Ultrasound in Parkinson's Disease: A Review. Schlesinger, I., Sinai, A., Zaaroor, M.[2020]

In a study of 10 patients (9 with essential tremor and 1 with Parkinson's), MRgFUS lesions were found to reach their maximum size and edema volume by day 3 post-treatment, with no serious complications like infarcts or hemorrhage observed.

The reduction in tremor correlated strongly with the shrinkage of the MRgFUS lesions over time, particularly between days 3 and 180, suggesting that monitoring lesion size could be important for assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI follow-up after magnetic resonance-guided focused ultrasound for non-invasive thalamotomy: the neuroradiologist's perspective. Keil, VC., Borger, V., Purrer, V., et al.[2021]

In a study of 48 patients with medically refractory tremor-dominant Parkinson's disease, MRgFUS thalamotomy provided significant and sustained tremor control over a follow-up period of up to 3 years.

The procedure was associated with mild side effects, such as gait imbalance and sensory deficits, which were mostly manageable and persisted in some cases, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort. Chua, MMJ., Blitz, SE., Ng, PR., et al.[2023]

In a study of 29 patients who underwent MRgFUS thalamotomy for tremor-predominant Parkinson's Disease, 96% experienced immediate tremor improvement, and 63% maintained this improvement at a median follow-up of 16 months, indicating the efficacy of this incisionless treatment.

Patient satisfaction was high, with 69% reporting improved quality of life, although 38% experienced mild long-term side effects, particularly related to speech when additional targeting of certain brain areas was performed, which did not enhance tremor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease. Maragkos, GA., Kosyakovsky, J., Zhao, P., et al.[2023]

In a study of 116 patients treated with magnetic resonance-guided focused ultrasound (MRgFUS) for hand tremor, significant reductions in tremor severity were observed at 3 months (84.5%), 6 months (79.8%), and 12 months (72.2%) post-treatment, indicating the procedure's efficacy.

While MRgFUS is effective, it is associated with adverse events such as gait imbalance and dysarthria, with some patients experiencing lasting effects; however, most side effects resolved within 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiating a Magnetic Resonance-Guided Focused Ultrasound Program: Comprehensive Workflow and Lessons Learned from the Initial 116 Cases. Zhang, DY., Pearce, JJ., Mazza, J., et al.[2023]

Magnetic resonance-guided focused ultrasound (MRgFUS) significantly improved limb tremor and daily activities in Parkinson's disease patients compared to a sham procedure, based on a pooled analysis of 2 studies with treatment durations of up to 4 months.

While MRgFUS was associated with some adverse events, such as dizziness, there were no serious side effects reported, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials. Ge, Y., Wang, Z., Gu, F., et al.[2022]

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