Noninvasive Spinal Cord Neuromodulation to Enhance Motor Function in Individuals with Hereditary Spastic Paraplegia

Abstract Hereditary Spastic Paraplegia (HSP) refers to a group of chronically disabling, neurodegenerative disorders that affects men and women of all ages, and presents as spasticity and weakness in the lower limbs, often accompanied by urine urgency and leakage. The individuals with complex forms of HSP can also suffer from seizures, cognitive decline, and peripheral neuropathy. With an estimated global prevalence of 1.2 to 9.6 per 100,000 individuals, at least 5 of 100,000 Americans currently live with HSP. These complications not only erode physical independence but also profoundly impact communication, cognition, and dignity, turning what is already a life-altering motor disorder into a multisystem neurodegenerative condition with devastating consequences for both patients and caregivers. Current management of HSP is limited to symptomatic treatment, including spasticity-reducing medications, physical therapy and in extreme cases, surgery; all aimed at slowing down the progression of spasticity and loss of mobility. These interventions offer only modest and temporary relief, leaving patients to face a progressive decline in function with no hope of altering the disease course. Although preclinical studies have identified promising molecular targets, no therapies have successfully translated to clinical use. This reflects a critical and urgent need for non-invasive, disease-modifying interventions that can restore function and improve quality of life. Spinal cord stimulation (SCS) has shown promise in reducing spasticity and restoring function in a number of neurological conditions such as spinal cord injury, cerebral palsy, multiple system atrophy and stroke. Encouragingly, two case reports have demonstrated the functional benefit of SCS in individuals with HSP. These data, along with the mechanistic overlap and the known safety and scalability of tSCS, support the rationale for investigating its therapeutic potential in HSP. As a new investigator with over 40 peer-reviewed publications, I am strongly motivated to pursue this line of research based on clinical need and direct encouragement from Norma Pruitt, Executive Director of the Spastic Paraplegia Foundation, as well as from numerous patients who have expressed a clear willingness to participate in such a trial.