Targeted neuromodulation therapies of the spinal cord to alleviate gait deficits in Parkinson’s disease

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders, affecting one to two percent of the population over sixty years old. Although it is usually associated with tremor, rigidity and slowness of movements, deficits of gait and balance deteriorate with disease progression and become a major source of disability. Additionally, although only a minority are affected at the early stages of the disease, most patients with PD will develop a very incapacitating condition called freezing of gait (FOG) during which they suddenly are unable to move forward, as if their feet are “glued to the ground”. The resulting loss of mobility and independence leads to a decline in quality of life and higher mortality rates due to increased risk of falls and subsequent injuries. Many motor signs are efficiently treated by dopaminergic medication and deep brain stimulation (DBS) of basal ganglia structures. Although patients can also experience temporary locomotor improvements, in most cases available neuromodulation therapies fail to alleviate or can even aggravate gait and balance deficits. Years after implantation, as their burden continues to rise while cardinal symptoms remain partially stable, locomotor symptom reduction remains a therapeutical challenge. Developing novel strategies to address this unmet need and getting insights into the mechanisms underlying control of gait in PD is the pivot of my thesis. Besides the brain, the spinal cord can also be a target to improve body functions. Its ability to integrate sensory and supra-spinal information can be leveraged to develop neuromodulation therapies. Throughout the last decade, Epidural Electrical Stimulation (EES) of the spinal cord has been proposed as a possible solution for improving locomotor performance in patients with PD. Pre-clinical studies showed promising results by delivering continuous stimulation at the thoracic level of the spinal cord, however translation to patients with PD led to inc