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In this context, urinary exosomal miRNAs could be an appealing source of biomarkers, thanks to their non-invasive and easily repeatable collection. Methods: In this exploratory investigation, we tried to assess if profiling urinary exosomal miRNAs could reveal subtle differences within an apparently homogeneous MS population. The study involved 24 patients with primary or secondary progressive MS, whose urinary exosomes (UEs) were subjected to evaluation of a panel of 87 miRNAs variously correlated with neuroinflammation, cardiovascular functions, and\/or involved in MS. Results: We revealed that the examined miRNAs were heterogeneously expressed across the patients, reflecting, as expected, their gender and\/or hormonal status. Two miRNAs discriminated against primary or secondary progressive MS, and a panel of 14 commonly upmodulated miRNAs identified patients with longer disease duration and a greater degree of disability. Conclusions: Even if preliminary, these data represent the first relationship between UEs and MS features in humans and suggest that urine could constitute a non-invasive source of exosomal miRNAs, which could prove useful in complementing conventional monitoring to provide a more personalized management of MS patients.<\/jats:p>","DOI":"10.3390\/ncrna12030016","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:35:43Z","timestamp":1778528143000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Exosomal microRNAs as a Novel Approach to Study People with Multiple Sclerosis and Severe Gait Disability: A Preliminary Observation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8502-4498","authenticated-orcid":false,"given":"Silvia","family":"Grassilli","sequence":"first","affiliation":[{"name":"Department of Environmental Sciences and Prevention and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-3090","authenticated-orcid":false,"given":"Andrea","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Unit of Physical and Rehabilitation Medicine, University Hospital of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-8674","authenticated-orcid":false,"given":"Marina","family":"Pierantoni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Brugnoli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-3069","authenticated-orcid":false,"given":"Nicola","family":"Lamberti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-9922","authenticated-orcid":false,"given":"Sofia","family":"Straudi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Unit of Physical and Rehabilitation Medicine, University Hospital of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9476-6434","authenticated-orcid":false,"given":"Fabio","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Program of Vascular Rehabilitation and Exercise Medicine, University Hospital of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Bertagnolo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","first-page":"14","article-title":"Multiple Sclerosis: 2024 Update","volume":"6","author":"Klotz","year":"2025","journal-title":"Free Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s44197-025-00353-6","article-title":"Epidemiology of Multiple Sclerosis: Global, Regional, National and Sub-National-Level Estimates and Future Projections","volume":"15","author":"Khan","year":"2025","journal-title":"J. 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