The Food and Drug Administration’s recent approval of staged bilateral focused ultrasound for the treatment of advanced Parkinson’s disease expands the therapeutic options available for patients with symptoms that cannot be controlled by medication.
Focused ultrasound is a noninvasive approach to brain surgery that uses ultrasound waves to precisely ablate tissue, allowing surgeons, who are guided by MRI, to target areas of the brain that affect movement disorder symptoms. The bilateral approach is already approved for the treatment of essential tremor; for Parkinson’s disease, the FDA first approved unilateral use in 2018 for tremor-dominant Parkinson’s, then expanded approval in 2021 for mobility issues, rigidity, bradykinesia and dyskinesia due to advanced disease. The current approval marks the first time Parkinson’s patients can receive focused ultrasound on both sides of the brain.
The bilateral approach gives physicians another way to tackle the multiple symptoms that many Parkinson’s patients must live with. “A lot of the patients we’ve treated over the years accepted tremor as their main symptom, and felt that if we got that under control — even if we couldn’t improve the other symptoms — that would be enough,” says Michael Kaplitt, M.D., Ph.D., a neurosurgeon at NewYork-Presbyterian and Weill Cornell Medicine and vice chair for research in the Department of Neurological Surgery at Weill Cornell Medicine, who was the lead investigator in the clinical trial that led to the FDA’s decision. “Now with this new FDA approval, we don't necessarily have to make that choice. It’s a new era.”
The Benefits of a Bilateral Approach
Most Parkinson’s disease patients can control their symptoms with medication, but for those who cannot tolerate medications or who experience increasing resistance to these therapies, surgical options may be appropriate.
“Deep brain stimulation, which we’ve been doing at this institution for decades, had been the most common brain surgery to manage the freezing and tremor-related symptoms of Parkinson’s,” says Dr. Kaplitt. This approach involves implanting into the brain an electrode that is connected via wiring to a pulse generator, which is implanted underneath the skin of the chest. “This equipment must be maintained over time, there can be mechanical issues, and as with any surgery, it carries a risk of infection. Many patients would like an option that allows them to potentially avoid these issues, and focused ultrasound provides an important new alternative for those who are candidates for the procedure.”
By the time a medication is no longer effective, most patients have reached a point where symptoms are prominent on both sides. This makes bilateral treatment of much greater value to these patients.
— Dr. Michael Kaplitt
Unilateral focused ultrasound marked a major step forward, but it only enables surgeons to fix symptoms in the dominant hand; those with bilateral symptoms would still experience tremors or rigidity in their nondominant hand. “There are patients with symptoms on only one side who would benefit from one-sided surgery, but they tend to be earlier-stage patients,” says Dr. Kaplitt. “By the time a medication is no longer effective, most patients have reached a point where symptoms are prominent on both sides. This makes bilateral treatment of much greater value to these patients.”
Future Applications for Focused Ultrasound
NewYork-Presbyterian’s experience in focused ultrasound — the institution recently completed its 500th procedure — puts it at the forefront of this evolving technology. Dr. Kaplitt was the first neurosurgeon in New York to use the procedure to treat essential tremor, and he continues to lead clinical trials for its use in movement disorders, with plans to further expand the scope of noninvasive brain surgery.
For example, at lower energy levels, focused ultrasound could be used to disrupt the blood-brain barrier to better deliver medications, such as chemotherapy or gene therapies, directly to the brain. It can also be used for neuromodulation, which changes the biology of the targeted brain tissue.
“With neuromodulation, you’re changing the function of that tissue in the brain,” says Dr. Kaplitt. “Researchers are currently running trials using focused ultrasound in the areas of the brain responsible for addiction, reward, and satisfaction, and they have seen improvement in patients with opiate addiction.” Dr. Kaplitt and his colleagues in psychiatry are currently preparing to start a clinical trial at NewYork-Presbyterian and Weill Cornell Medicine that tests neuromodulation for this use case.
“When focused ultrasound was introduced, we saw it as the future for treatment of movement disorders and beyond,” says Dr. Kaplitt. “I am fortunate to be in an institution where everybody believes in this and is trying to push the envelope, and that's why we continue to lead the way in this field.”
