{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:24Z","timestamp":1790657964653,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hypermobile Type Ehlers-Danlos Syndrome (hEDS) accounts for 80%\u201390% of all Ehlers-Danlos cases. hEDS pathophysiology is uncertain. There is no diagnostic test. Symptoms include joint hypermobility, intractable and debilitating joint pain, chronic fatigue, brain fog, irritable bowel symptoms and mast cell activation syndrome. Treatment options are limited and ineffective. None are disease-modifying. This pilot study evaluated the safety and potential for efficacy of a novel biologic investigational product (IP) comprising an extracellular vesicle enriched secretome from human bone marrow-derived mesenchymal stem cells (hbm-MSC EVs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Ten (10) hEDS patients were recruited and treated with up to four doses of IP by intravenous infusion for up to five months. Symptoms were assessed using a custom 9-criteria questionnaire addressing common symptoms and by observation at each infusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No treatment related adverse events were reported or noted. Statistically significant response was found before treatment and after treatment for the ten patients as a group. However, six (6) out of the ten (10) patient exhibited distinct, substantial, rapid, and sustained overall improvement of their symptoms within the study time frame. Due to time limitations of the study, a single distinct responder (one of six responders), with IND approval for continued treatment, was further treated and observed for an additional twelve (12) months. Treatment was ultimately stopped at the patient's request and for 32 months thereafter has lived in apparent remission without pain or any previous symptoms or signs of Hypermobile Ehlers-Danlos Syndrome. All five (5) prior distinct responders with discontinued treatment reverted to their pre-treatment condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Results of this pilot study suggest that a randomized, controlled trial is warranted to evaluate the potential of the IP for treatment of hEDS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1945865","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:36:53Z","timestamp":1790656613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A trial of exosome rich stem cell secretome as a potential treatment for Hypermobile Ehlers-Danlos Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Kevin J.","family":"Flynn","sequence":"first","affiliation":[{"name":"Independent Researcher","place":["Austin, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Ransom","sequence":"additional","affiliation":[{"name":"Direct Biologics , Medical Affairs","place":["Austin, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McGrath","sequence":"additional","affiliation":[{"name":"McGrath Medical","place":["Austin, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","article-title":"Hypermobile ehlers-danlos syndrome","volume-title":"Genereviews\u00ae","author":"Hakim","year":"2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the ehlers-danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"B3","article-title":"Ehlers-danlos syndrome","volume-title":"Statpearls","author":"Miklovic","year":"2024"},{"key":"B4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/ajmg.c.31538","article-title":"Hypermobile ehlers-danlos syndrome (A.K.A. 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