Study Rationale:
People with advanced Parkinson’s disease often develop severe gait and balance impairments—including asymmetries, instability, and freezing of gait—that are heterogeneous, episodic and task-dependent. These deficits often emerge during activities requiring physical or cognitive effort, such as navigating busy or confined spaces, or when engaging in multi-tasking. They are also influenced by contextual factors like attention, fatigue or stress. Standard deep brain stimulation (DBS) therapies, which deliver stimulation continuously, are intrinsically unable to address the episodic nature of gait impairments. This may explain their limited and variable efficacy. Instead, therapies that adapt the delivery of stimulation in real-time, aligned to the emergence of deficits, may more effectively prevent FOG episodes, loss of balance, gait asymmetry or initiation difficulties.
Hypothesis:
We hypothesize that gait-targeted adaptative DBS protocols, synchronized to neural biomarkers of gait, actively suppresses the pathological neuronal dynamics underlying impaired locomotion, thus better alleviating gait and balance deficits.
Study Design:
We will conduct a feasibility clinical trial on 20 people with PD (trial duration: 24 month) to evaluate the safety and preliminary efficacy of gait-targeted aDBS therapies. Recruited participants will exhibit severe gait deficits, refractory to standard treatments, and be implanted with a Percept PC DBS implant (we already obtained regulatory approval from the Swiss authorities, Kofam SNCTP000006185). For each participant, we will (i) validate that gait-targeted aDBS therapy robustly modulates pathological neural signatures in real-time and alle-viates gait deficits, and (ii) demonstrate that these improvements are sustained over time and translated to everyday settings, beyond well-controlled clinical environments.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
For decades, DBS therapies have been optimized for cardinal motor symptoms such as rigidity and bradykinesia with highly successful results. However, the efficacy of these interventions for gait and balance problems has been inconsistent, and in cases even detrimental. ADAP GAIT will give answer to this therapeutic gap. It will leverage the capabilities of new-generation DBS neurostimulators and adapt DBS delivery in real-time to the spatiotemporal specificities of locomotion, thus alleviating gait deficits more robustly.
Next Steps for Development:
Following this feasibility trial, we will work with the manufacturer to validate and deploy gait-targeted aDBS therapies under the framework of a pivotal, multicenter clinical trial involving up to 100 participants across four sites. We will further use trial data to identify neurological response profiles, that will inform patient selection criteria and enable more personalized stimulation protocols, increasing the therapy’s effectiveness and scalability.