Spinal-cord stimulation technologies and methods to alleviate gait deficits of Parkinson's disease – PDWALK

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, affecting more than ten million people worldwide. More than 90% of individuals with PD suffer from locomotor disturbances that affect their quality of life and increase comorbid conditions. Contrary to upper-limb motor symptoms, these deficits respond poorly to commonly available therapies such as dopamine replacement strategies and deep brain stimulation (DBS). The divergence in the nature and dynamics of the circuits that control manual dexterity versus locomotion may explain why gait deficits are resistant to treatments optimized for upper-limb motor symptoms. Consequently, we propose to target the circuits in the spinal cord that are directly responsible for the production of locomotion. Previous studies reported gait improvements during continuous stimulation of the dorsal columns at the thoracic level of the spinal cord, but the results have been inconsistent and variable. Here, we will pursue a radically different strategy focused on the modulation of the locomotor circuits within the lumbar spinal cord. We will leverage our newly-designed spinal-cord stimulation technology that has been conceived to recruit the individual posterior roots of the lumbar spinal cord in order to modulate the spinal circuits involved in the control of leg movements. This technology combines a multi-electrode array targeting lumbar posterior roots, connected to an implantable pulse generator controlled wirelessly and in real-time by devices that infer user’s movement intentions. The sequential recruitment of the lumbar posterior roots with a precise timing that coincides with the ongoing patient’s movement intentions reinstates the natural dynamics of lumbar motor circuits. We showed that this technology restored walking in nine individuals with paralysis due to spinal cord injury, and alleviated gait and balance deficits in the gold-standard nonhuman primate model of PD. Here, we will evaluate the ability of our spinal-cord stimulation technologies and methods to alleviate gait/balance deficits and freezing-of-gait in patients with PD whose locomotor deficits resist to pharmacological and DBS treatments. We will study both the immediate and long-term impact of spinal-cord stimulation, DBS, and gait rehabilitation on locomotor performance using high-resolution biomarkers: continuous recordings of gait kinematics and subthalamic nucleus activity in real-life settings. Our goal is to develop a treatment that alleviates gait and balance deficits and durably improves the neurological condition of people with PD.