Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system with limited treatment efficacy for progressive forms. Mesenchymal stem cells (MSCs) and their secreted exosomes offer therapeutic potential via regenerative and immunomodulatory actions, including T-cell suppression and neurotrophic factor secretion. Exosomes, as cell-free alternatives, may mediate MSC effects by delivering cargo such as microRNAs, potentially promoting oligodendrocyte precursor cell differentiation and blood-brain barrier stabilization with reduced immunogenicity. Preclinical experimental autoimmune encephalomyelitis models and early MSC clinical trials demonstrate promise in reducing disease severity, although optimization of exosome sources, delivery routes (intrathecal versus intravenous), dosing, and standardization remains a challenge for clinical translation. Here, we describe a 44-year-old female with a 21-year history of progressive MS unresponsive to interferon beta-1a and Ocrelizumab, who presented with widespread neurological deficits, including sensory disturbances, weakness, and urge incontinence. Examination revealed ataxia, intention tremor, and hyperreflexia, with previous MRIs confirming MS plaques. In 2025, she received allogeneic umbilical cord-derived MSC exosomes (1 cc intrathecally; 1 cc intravenously at half dose) with adjunctive intravenous laser therapy. Within three weeks, she reported 70-80% symptomatic improvement, including resolution of Lhermitte's sign and enhanced muscle strength, vision, memory, and energy. Two-month follow-up MRIs showed persistent lesions without new contrast enhancement, indicating no active disease progression. This case highlights significant symptomatic improvement in long-standing progressive MS following combined intrathecal and intravenous allogeneic UC-MSC exosome administration. The rapid clinical benefits and absence of new MRI activity suggest a potential modulatory role for exosome therapy in MS, although these encouraging findings from a single case with adjunctive therapy necessitate larger, controlled clinical trials to validate efficacy, safety, and optimal protocols, and to elucidate underlying mechanisms.
