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With no disease-modifying therapies available, novel strategies to improve motor function are needed. Transcutaneous spinal cord stimulation (tSCS) is a non-invasive neuromodulation approach that may improve motor function but has not been prospectively evaluated in HSP. This study will assess the safety, feasibility, and preliminary efficacy of repeated tSCS in adults with HSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This prospective, open-label, single-arm pilot trial will enroll 15 adults with HSP. Participants will receive 16 tSCS sessions over 8 weeks targeting the lower thoracic and upper lumbar vertebral levels, followed by an 8-week follow-up. Outcomes will assess gait performance, spasticity, disease severity, mobility, walking endurance, muscle strength, 3D gait biomechanics, electromyography, and HSP-specific patient-reported measures. Exploratory blood-based neurodegenerative biomarkers and metabolomic and lipidomic profiles will investigate potential biological correlates of treatment response. Assessments will occur at baseline and weeks 4, 8, and 16. Feasibility and safety will be evaluated through recruitment, retention, adherence, and adverse events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0359948","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:32:26Z","timestamp":1792085546000},"page":"e0359948","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcutaneous spinal cord stimulation for functional recovery in individuals with hereditary spastic paraplegia: Protocol for a pilot clinical trial"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4612-6138","authenticated-orcid":true,"given":"Vivek K.","family":"Pandey","sequence":"first","affiliation":[{"name":"University of Kentucky","place":["Lexington, United States of America"],"department":["Department of Physical Medicine and 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Kentucky","place":["Lexington, United States of America"],"department":["Spinal Cord and Brain Injury Research Center (SCoBIRC)"]},{"name":"University of Kentucky","place":["Lexington, United States of America"],"department":["Department of Physiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Gad","sequence":"additional","affiliation":[{"name":"SpineX Inc","place":["Los Angeles, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rich","family":"Cohn","sequence":"additional","affiliation":[{"name":"Independent Consultant","place":["Chapel Hill, North Carolina, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron G.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Person with Lived Experience","place":["Lexington, United States of 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Physiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara S.","family":"Salles","sequence":"additional","affiliation":[{"name":"University of Kentucky","place":["Lexington, United States of America"],"department":["Department of Physical Medicine and Rehabilitation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6594-6213","authenticated-orcid":true,"given":"Zakari R.","family":"Dymock","sequence":"additional","affiliation":[{"name":"University of Kentucky","place":["Lexington, United States of America"],"department":["Department of Physical Medicine and Rehabilitation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0597-1159","authenticated-orcid":true,"given":"Michael A.","family":"Samaan","sequence":"additional","affiliation":[{"name":"University of Kentucky","place":["Lexington, United States of America"],"department":["Department of Kinesiology and Health 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