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With a mean onset age of 37\u201343\u2009years, PPMS affects 10%\u201315% of MS patients and presents distinct diagnostic and treatment issues. Mobility issues, persistent pain, sensory disturbances, cognitive deficits, and bowel and bladder problems intensify over time. Neuroimaging shows substantial brain and spinal cord atrophy with fewer brain lesions but more spinal cord lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Drugs like ocrelizumab reduce progression, whereas high\u2010dose biotin, simvastatin, and coenzyme Q10 are being investigated. PPMS treatment is difficult, with continuing research on fingolimod, idebenone, anti\u2010LINGO\u20101, neuromodulation, and plasmapheresis. Ocrelizumab has shown encouraging outcomes. Preclinical gene therapy studies on immune regulation, neuroprotection, and remyelination in MS animals show promise. Hematopoietic and non\u2010hematopoietic stem cell therapies have also been studied for their capacity to reduce neuroinflammation, repair tissue, and boost neurotrophic support.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinical research utilizing human fetal neural precursor cells (hfNPCs) reveals neuroprotective advantages and opportunities for PPMS treatment. Early clinical trials have shown promising results, but more study is needed to prove the safety and usefulness of these new PPMS treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70039","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T03:13:41Z","timestamp":1752462821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Primary Progressive Multiple Sclerosis: New Therapeutic Approaches"],"prefix":"10.1002","volume":"45","author":[{"given":"Morteza","family":"Rajabi","sequence":"first","affiliation":[{"name":"Department of Genetics, Faculty of Basic Sciences, Central Tehran Branch Islamic Azad University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Shafaeibajestan","sequence":"additional","affiliation":[{"name":"Shared Health \u2013 Northern Regional Health Authority (NRHA)  Flin Flon Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevda","family":"Asadpour","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, School of Medicine Hamadan University of Medical Sciences  Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazal","family":"Alyari","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Advanced Technologies in Medicine Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Department of Medical Genetics and Molecular Medicine, School of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloofar","family":"Taei","sequence":"additional","affiliation":[{"name":"Department of Microbiology Islamic Azad University of Damghan  Damghan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moein","family":"Kohkalani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Raoufinia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Molecular Medicine, School of Medicine Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Noncommunicable Diseases Research Center Neyshabur University of Medical Sciences  Neyshabur Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Afarande","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Molecular Medicine, School of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-1068","authenticated-orcid":false,"given":"Ehsan","family":"Saburi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Molecular Medicine, School of Medicine Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Medical Genetics Research Center Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13819"},{"key":"e_1_2_20_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.26858"},{"issue":"3","key":"e_1_2_20_4_1","first-page":"175","article-title":"Multiple Sclerosis Review","volume":"37","author":"Goldenberg M. 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