Dual-Target Focused Ultrasound Delivers Immediate Relief in Advanced Parkinson's as Bilateral PTT Data Back FDA Approval
核心洞察
CU Anschutz (搜索) clinicians performed the Rocky Mountain region's first dual-target HIFU procedures, targeting the DRTT and PTT tracts six to nine millimeters apart in two advanced Parkinson's patients.
The female patient achieved zero tremor and roughly 70% improvement in stiffness and movement speed after the PTT ablation, with benefits evident immediately on the MRI table.
An international trial published in Lancet Neurology reported 32% improvement in cardinal motor symptoms and 67% improvement in motor complications three months after bilateral PTT treatment.
A high-intensity focused ultrasound (搜索) (HIFU) procedure that targets two brain tracts just six to nine millimeters apart has produced immediate motor symptom relief in two patients with advanced Parkinson's disease (搜索), in what the Advanced Therapies in Movement Disorders (ATMD) Program at CU Anschutz (搜索) described as the first dual-target HIFU procedures performed in the Rocky Mountain region.
The treatments were led by Drew Kern, MD, MS, associate professor of neurology, and Daniel Kramer, MD, associate professor of neurosurgery, both at the CU Anschutz (搜索) School of Medicine. One female patient began walking with a more fluid gait, while a male patient with dementia was able to eat breakfast without difficulty for the first time.
"We did it one week, and it worked great," Kern said of the dual-target procedure performed on the woman. "Then we thought about it for another patient – a man who had dementia. And sure enough, afterward he had zero rigidity and very little slowness of movement, plus no tremor. His wife said that was the best night of sleep they've had in years because he wasn't having a tremor. And, for the first time, he actually ate breakfast without any difficulty."
Two Targets, One Outpatient Session
The dual-target approach combines ablation of the dentatorubral thalamic tract (搜索) (DRTT), which regulates tremor movements, and the pallidothalamic tract (搜索) (PTT), an area that when compromised causes stiffness, slowness of movement and involuntary movement. Both targets were treated in the same outpatient procedure, which took about 90 minutes.
During the DRTT portion, the female patient experienced roughly 60–70% improvement in her rest tremor, with little improvement in stiffness and slowness of movement. After the PTT procedure, "she got the full benefit and had zero tremor. In addition, she had, I would estimate at least 70% improvement of stiffness and about the same with the speed of her movements," Kern said, adding that the beneficial results were immediate on the MRI table.
The FDA first approved HIFU for tremor-dominant Parkinson's disease (搜索), which affects approximately 10–20% of the Parkinson's population, delivering ultrasound waves to the DRTT. More recently, the agency approved HIFU for the PTT, extending the approach to symptoms beyond tremor, including rigidity and bradykinesia. Dyskinesia, or involuntary movement, and bradykinesia, or slowness of movement, are among the motor complications affecting people with advanced Parkinson's disease. More than 1.2 million Americans have Parkinson's, a progressive neurological disorder with no cure.
The ATMD team has treated more than 100 patients with the DRTT target, according to Kern, with patients showing significant tremor improvement. "The outcomes support sustained benefit for at least five years as this treatment has only become more widely used over that period," he said. "As time goes on, we will be able to evaluate even longer outcomes."
Neither HIFU patient was a viable candidate for deep brain stimulation (DBS), the long-established surgical option in which electrodes are implanted in a targeted brain area. "For any individual who isn't really a great candidate for DBS, this might give them another option, another hope," Kern said. HIFU is an incisionless, ablative-focused procedure that interrupts the circuitry causing motor symptoms, and has become available in recent years for patients with advanced Parkinson's who have not found relief from medications and are not DBS candidates due to infection risk and other reasons.
Bilateral Trial Data Underpin 2025 Approval
The dual-target work builds on prospective, multicenter evidence for staged bilateral PTT treatment. According to a publication in Lancet Neurology, participants in an international trial experienced a 32% improvement in cardinal motor symptoms three months after bilateral treatment, with benefits sustained through follow-up. Motor complications — movement-related side effects from Parkinson's medications — improved by 67%.
The trial (NCT04728295) is the first to systematically evaluate staged, bilateral focused ultrasound treatment in Parkinson's disease (搜索). Researchers at six centers in the US, two in Spain, and one in Taiwan targeted the PTT using bilateral MR-guided focused ultrasound with the Insightec Exablate Neuro (搜索) device. Fifty-four participants (37 male and 17 female, average age 63 years) were treated on the symptom-dominant side; after at least six months, 40 of the 54 met criteria for treatment of the other side of the brain, and 36 participants completed 12 months of follow-up after the second procedure.
Unilateral PTT focused ultrasound was shown to be safe and efficacious for improving motor symptoms and motor complications. Motor function further improved after treatment of the second side, though the incremental benefit was less pronounced. Adverse events occurred in 39% of participants after unilateral treatment and 55% after bilateral treatment. One clinically significant event persisted at six months after the first procedure, and ten events persisted for at least one year after the second procedure. The publication recommends that physicians exercise rigorous patient selection and counseling regarding cumulative risks before offering second-side PTT treatment.
"This study represents an important milestone in the evolution of focused ultrasound treatment for PD and highlights the need for additional studies to confirm the effectiveness of the treatment and develop approaches to minimize its side effects," said Foundation chairman Neal F. Kassell, MD. The study was funded by Insightec.
These data were considered by the FDA in its 2025 approval of unilateral and staged, bilateral focused ultrasound for advanced Parkinson's disease (搜索). According to Insightec, more than 30,000 patients have been treated with the Exablate device for a variety of movement disorder indications at 214 centers worldwide, including more than 100 locations in the US.
Durability and Cognitive Questions Remain
Longer-term outcomes with PTT continue to be studied, including possible cognitive effects, and further study is needed to determine HIFU's durability and the merits of a bilateral treatment approach. The two CU Anschutz (搜索) patients will return for follow-up visits in a couple of months.
The FDA requires that patients who have undergone HIFU on one side wait at least six months before a second-side procedure. The ATMD program has so far performed only unilateral HIFU. "We need more studies to convince us that doing a bilateral PTT HIFU is in a patient's best interest," Kern said. "It's something we certainly would have to discuss as a team."