Responsive, Closed-Loop Approach to Treat Freezing of Gait in Parkinson’s Disease

Study Rationale:                   
Levodopa-resistant posture, gait and freezing symptoms are among the most disabling and difficult to treat in people with Parkinson’s disease (PD). Recent findings from deep brain stimulation (DBS) trials have been promising for addressing many aspects of PD, but have failed to identify a therapeutic benefit for freezing and/or falling. We believe there are two critical brain areas that are not functioning in concert in PD and that their dysfunction may lead to freezing of gait. We aim to uncover the underpinning changes in the circuitry between these brain regions — globus pallidus interna (GPi) and pedunculopontine nucleus (PPN) — that may lead to freezing of gait in order to develop a DBS system to target this symptom.

Hypothesis:
We posit that we can develop a “smart” DBS system that will monitor the GPi and the PPN (and the network between them), and deliver electrical pulses necessary to address freezing episodes in real time.

Study Design:
We will simultaneously implant bilateral GPi and bilateral PPN DBS leads in five people with PD (with freezing while on medication). We will connect the DBS leads to a new technology (Medtronic PC+S) and monitor the real-time physiology of the brain network during walking and freezing. We will also utilize a novel technology to provide a rapid, automated closed-loop approach to break freezing episodes.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
We have chosen the troublesome symptom of on-medication freezing of gait, which currently has no optimal treatment option. If successful, this treatment may lead to improved quality of life for those who live with this symptom.

Next Steps for Development:
The neuromodulatory approach proposed in this application will provide an immediately deployable solution for freezing of gait, and results from this project can possibly be moved into a larger clinical trial. In addition, this study will provide a significant enhancement of our understanding of the basic circuitry underlying gait issues and freezing in PD.