Pivotal Trial Results of Focused Ultrasound for Parkinson’s Disease Published in the 'New England Journal of Medicine'


Key Points

  • Results from a multicenter, international clinical trial of focused ultrasound to address the major motor symptoms of Parkinson’s disease (PD) were published this week.
  • Three months after treatment, 69% of participants responded to the therapy, compared with 32% of patients in the sham cohort.
  • After one year, the majority of participants who showed a response at the 3-month follow-up experienced sustained results.
  • These data contributed to the US FDA expanding approval of focused ultrasound to include the treatment of patients with advanced PD suffering with mobility, rigidity, or dyskinesia.

The results of a multicenter pivotal clinical trial of MR-guided focused ultrasound to address the major motor symptoms of Parkinson’s disease (PD) have been published by the New England Journal of Medicine. The study data were considered when the US Food and Drug Administration (FDA) expanded approval of Insightec’s Exablate Neuro focused ultrasound device to include the treatment of patients with advanced PD suffering with mobility, rigidity, or dyskinesia.

Focused ultrasound uses ultrasound energy guided by real-time imaging to treat tissue deep in the body without incisions or radiation. Insightec’s Exablate Neuro is a helmet-like device that emits ultrasound waves and focuses them to target the part of the brain associated with these symptoms of PD.

The clinical trial evaluated 94 patients with advanced and medication-refractory PD. The trial took place at five sites in the US as well as locations in Canada, Japan, and Korea, and was led by Howard Eisenberg, MD, the Raymond K. Thompson Professor of Neurosurgery at the University of Maryland School of Medicine and a neurosurgeon at the University of Maryland Medical Center. It was sponsored by Insightec.

Physicians conducting this study performed a unilateral pallidal ultrasound ablation to improve motor function and reduced the dyskinesia symptoms associated with PD. Participants were randomly assigned, in a 3:1 ratio, to undergo either focused ultrasound ablation or a sham procedure. Those who received the sham procedure could cross over to the treatment arm after the 3-month blinded phase.

After three months, 45 of the 65 treated participants who completed the scheduled follow-up responded to the therapy (69%) according to a PD rating scale. Only 7 of the 22 (32%) in the control group responded, and this difference was statistically significant. In the treatment group, 30 of 39 participants (77%) who had a response at three months and who were available for follow-up at 12 months continued to have a response at 12 months. Pallidotomy-related adverse events were temporary in duration and were of mild or moderate intensity. These adverse events included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.

“Focused ultrasound ablation provides an option to patients who are unwilling to undergo the current standard-of-care treatment – deep brain stimulation – because they consider it too intrusive or risky,” said Dr. Eisenberg. “In addition, this study provides evidence that adverse events were generally uncommon, or if they did occur, they were usually mild and transient.”

These results build on data from the preliminary clinical trial, which was jointly funded by the Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and Insightec. The results of the early-stage trial were published in 2020 in the Journal of Neurosurgery.

“The Foundation has long considered neurological diseases to be the vanguard target for focused ultrasound, because of the complexities involved with treating the brain,” said Foundation Chairman Neal F. Kassell, MD. “We are proud to have supported the research that produced the initial data and led this pioneering and international team to leverage those results into an approved treatment that is changing lives. We remain champions of this technology and are actively funding research to expand focused ultrasound’s potential beyond symptom improvement for patients with PD.”

The authors stated that longer and larger trials will be needed over time to determine the safety and long-term effects of focused ultrasound pallidotomy in patients with PD dyskinesia.

“This is the largest surgical randomized controlled trial for PD,” said Vibhor Krishna, MD, Associate Professor of Functional Neurosurgery at the University of North Carolina School of Medicine. “These results are practice-changing and will establish focused ultrasound technology as an essential modality to treat the disease. We remain highly engaged in further optimizing this treatment to maximize clinical benefits and reducing any side effects.”

“This trial study group is now engaged in a bilateral treatment trial,” explained Dr. Eisenberg. “As symptoms of PD mostly affect both sides of the body, we are hopeful that this bilateral trial will demonstrate even greater efficiency while still maintaining an acceptable margin of safety.”

It is important to note that since the FDA approved focused ultrasound treatment for the mobility, rigidity, or dyskinesia symptoms associated with PD in 2021, the procedure is not yet widely reimbursed in the US. The majority of patients seeking this treatment are required to pay out-of-pocket at this time.

See the New England Journal of Medicine

About Focused Ultrasound for PD
In 2018, MR-guided focused ultrasound earned US Food and Drug Administration (FDA) approval to treat tremor-dominant PD using thermal ablation. This approval was expanded in 2021 to include patients with advanced PD suffering with mobility, rigidity, or dyskinesia symptoms. Importantly, this technique only offers relief from the debilitating symptoms of PD and does not address its underlying cause. Researchers are now exploring innovative techniques to use focused ultrasound to aid in the diagnosis, disease-monitoring, and even treating the underlying causes of PD.

Media Coverage

New Focused Ultrasound Effective for treating Parkinson’s, Movement Disorders | UNC Health

Incision-Free ‘Surgery’ Lowers Hard-to-Treat Parkinson’s Motor Symptoms | Parkinson’s News Today

Advanced Parkinson’s Symptoms Improved With Focused Ultrasound | Medpage Today