Pharmacologically modulating the noradrenergic ascending arousal system to reduce freezing of gait in parkinson’s disease: a multi-center multi-modal approach

Parkinson’s Research Project Title: Pharmacologically Modulating the Noradrenergic Ascending Arousal System to Reduce Freezing of Gait in Parkinson’s Disease: A Multi-Center Multi-Modal Approach

Principal Investigators: Dr. Jorik Nonnekes, Dr. Kaylena Ehgoetz Martens, Professor Simon Lewis, Dr. Melvyn Roerdink

Institutions: Radboud University Medical Center (Netherlands), Macquarie University (Sydney, Australia) and University of Waterloo (Canada)

Study Rationale:

Freezing of gait (FoG) is a common and debilitating symptom affecting 4 out of 5 people living with Parkinson’s disease. Despite its significant impact, no current Parkinson’s medication fully alleviates FoG. This symptom occurs when excessive cross-talk between brain regions disrupts movement control.

Atomoxetine, a medication commonly prescribed for ADHD, has been shown to reduce this excessive brain cross-talk. This study will investigate whether atomoxetine can reduce freezing severity in people with Parkinson’s and examine its effects on brain network activity using MRI imaging.

Participants with freezing of gait will be randomly assigned to receive either atomoxetine or a placebo and will undergo clinical walking assessments and augmented reality challenges designed to trigger and measure freezing episodes. Each participant will be assessed four times—in both medicated and unmedicated states—to evaluate the combined effects of dopamine treatment and atomoxetine.

If successful, this study could identify a much-needed pharmacological treatment for freezing of gait, improving mobility and quality of life for people with Parkinson’s. Given that atomoxetine is already an approved medication, positive results from this study could accelerate its clinical translation for Parkinson’s patients, leading to larger trials and potential regulatory approval.