- The results of an early-stage clinical trial investigating focused ultrasound to address a possible underlying cause of Parkinson’s disease were published in Movement Disorders.
- Researchers in Toronto tested the safety and efficacy of focused ultrasound–induced blood-brain barrier opening to deliver enzyme replacement therapy.
- The procedure was well-tolerated, and a larger study is being planned.
The results of a groundbreaking clinical trial investigating focused ultrasound to enhance drug delivery and address a possible underlying cause of Parkinson’s disease (PD) were recently published in Movement Disorders.
Researchers from Sunnybrook Health Sciences Centre and University Health Network (UHN) in Toronto used focused ultrasound to disrupt the blood-brain barrier (BBB) in patients with early-stage PD to deliver an enzyme replacement therapy called imiglucerase – or Cerezyme®.
The BBB is a protective layer of tightly joined cells that lines the blood vessels in the brain and prevents harmful substances, such as toxins and infectious agents, from diffusing from the blood into the surrounding brain tissue. However, it can also prevent beneficial therapeutic agents from getting into the brain in high enough concentrations to be effective. Focused ultrasound has been proven to safely and temporarily disrupt this barrier, and in this study, researchers aimed to open the BBB to allow delivery of the enzyme to the putamen – a key structure in the brain related to movement disturbances.
Some patients with PD can have a deficiency of a naturally occurring enzyme called glucocerebrosidase. Enzyme replacement therapy could be one approach to reduce or prevent neurodegeneration in PD.
“There are robust data in both preclinical and clinical studies demonstrating that glucocerebrosidase replacement is a promising disease-modifying therapy in Parkinson’s disease,” says Dr. Ying Meng, the study’s first author and a neurosurgery resident at the University of Toronto.
In the trial, four participants received three doses of the therapeutic plus focused ultrasound every two weeks to the side of the brain most affected by the disease. They were followed for three and six months. No significant adverse events were reported.
“We showed that focused ultrasound BBB opening can safely be combined with enzyme replacement therapy in PD, with promising, though very early, suggestions of biologic efficacy,” says Nir Lipsman, MD, PhD, the study’s co-principal investigator and director of Sunnybrook’s Harquail Centre for Neuromodulation. “Our findings are an exciting and critical first step in less invasive, direct-to-brain delivery of therapeutics to key areas of the brain important in the development and progression of PD.”
The trial was funded in part by the Focused Ultrasound Foundation.
“Focused ultrasound is an established therapy to help reduce the symptoms of PD, including tremor and dyskinesia, but this study is the first of its kind in aiming to treat the underlying cause of the disease and potentially stop progression or even reverse the neurological deficits,” said Foundation Chairman Neal F. Kassell, MD. “The researchers at Sunnybrook have been leaders in focused ultrasound for neurological conditions, and the Foundation is proud to support their work.”
Looking ahead, the Sunnybrook and UHN researchers have launched a Phase I/II clinical trial continuing the team’s investigation, which is set to start enrolling patients this fall.
“Our team is focused on next steps, collaborating with local and global partners on larger trials, and determining what impact we are having, if any, on disease progression,” added Dr. Lipsman. “The ultimate goal is nothing short of slowing the disease and improving the lives of our patients and their families.”