Focused Ultrasound for Parkinson’s Dementia: First-in-Human Data Published


Key Points

  • People living with Parkinson’s disease sometimes develop memory loss, forgetfulness, trouble concentrating, and eventually dementia.
  • A collaborative team of researchers led by Prof. José Obeso, MD, PhD, is seeking to use focused ultrasound to address this devastating complication.
  • The research team successfully used focused ultrasound to open the blood-brain barrier in people with Parkinson’s dementia, and the procedure was well tolerated.

Striatal Blood-Brain Barrier Opening in Parkinson’s Disease Dementia: A Pilot Exploratory Study

Although Parkinson’s disease is classified as a movement disorder, people with Parkinson’s disease sometimes develop memory loss, forgetfulness, trouble concentrating, and eventually dementia. Like other types of dementia, Parkinson’s dementia is debilitating and causes patients to be unable to care for themselves or perform simple daily tasks.

To prevent this devastating complication, a collaborative team of researchers based in Madrid and led by Prof. José Obeso, MD, PhD, is seeking to use focused ultrasound to help people with Parkinson’s avoid progression to dementia. Results from the group’s first-in-human study to open the blood-brain barrier (BBB) in a new region of the brain to address this problem were recently published in the journal Movement Disorders. These data provide yet another building block in a series of studies designed to help physicians become able to treat these patients earlier and more effectively.

In the phase I, single-arm, nonrandomized, proof-of-concept study (NCT03608553), investigators enrolled seven participants with Parkinson’s dementia to test the safety and feasibility of using focused ultrasound to open the BBB in the region of the brain called the striatum. Previous studies have determined that the neurotransmitter dopamine becomes reduced in the striatum in patients with Parkinson’s disease as the disease progresses. The team used Insightec’s Exablate Neuro device for the trial. Each participant underwent the BBB opening procedure twice, 2 to 4 weeks apart. After an addendum to the original protocol, three of the seven participants underwent bilateral BBB opening during the second session.

“The ultimate aim for using BBB opening for Parkinson’s disease will be to deliver putative, restorative, and neuroprotective agents to the striatum, which is where the damage occurs earliest and is most severe,” said Prof. Obeso. “These agents might be gene therapies, antibodies, anti-inflammatories, or other pharmaceuticals. The aim of this study, however, was to prove that we could perform repeated and bilateral focal BBB opening in the region where dopamine loss first occurs in patients with Parkinson’s disease. This provides the background for possible therapeutic studies going forward.”

Professor Obeso added, “At one of the first Foundation workshops on this topic, the representatives from the US Food and Drug Administration made it clear that we must first establish the safety of BBB opening before administering a therapeutic. Otherwise, it would not be clear which mechanism was creating a therapeutic benefit or a side effect. It was important to them to do this research in a step-by-step fashion, and this is one of those important steps toward designing a therapeutic trial.”

The research team determined the procedure was feasible and well tolerated. No serious adverse events occurred. MRI was used to confirm BBB opening and closing. The team also noted a small, but significant reduction in β-amyloid uptake in the targeted region.

With the successful completion of this pilot study, the group is planning a larger follow-up study and testing the possibility of administering a medication or a neurorestorative molecule across the BBB.

“Looking to the future, our goal is not to treat mainly Parkinson’s dementia,” said Prof. Obeso. “Our goal is to prevent Parkinson’s patients from ever developing dementia, and truly – someday, to prevent Parkinson’s from ever progressing at all, in any way. I would like to be able to treat patients with early Parkinson’s and to be able to diagnose the disease as early as possible to help more people.”

The clinical trial was funded by the MAPFRE Foundation and the Spanish Ministry of Education and Science. Early results from this trial were published in Nature Communications (February 2021).

See Movement Disorders >

Related Stories
Focused Ultrasound for Parkinson’s Disease: Meet the Experts April 2021

Fireside Chat: A Conversation with the Experts about Focused Ultrasound for Parkinson’s Disease April 2021

Focused Ultrasound for Blood-Brain Barrier Opening in Patients with Parkinson’s Dementia March 2021

Landmark Clinical Trial Shows Focused Ultrasound to be a Safe and Effective Treatment for the Cardinal Features of Parkinson’s Disease December 2020

Two Landmark Studies Advance Focused Ultrasound Treatment for Parkinson’s Disease October 2020

Parkinson’s Trial in Madrid Investigates Treating a New Target April 2018