{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T05:58:55Z","timestamp":1671688735790},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aging frailty (AF) is a multidimensional geriatric syndrome that is characterized by physical and cognitive symptoms, increasing the vulnerability of affected older adults to adverse health outcomes. Mechanistically, a low-grade chronic inflammatory state (inflammaging), endothelial dysfunction, and decreased regenerative capacity are thought to be major contributors to AF pathophysiology. Lomecel-B is an allogenic medicinal signaling cell(MSC) formulation that can potentially ameliorate AF through pleiotropic mechanisms, including anti-inflammatory, pro-vascular, and pro-regenerative activities. We completed a Phase 2b randomized, double-blinded, placebo-controlled trial designed to assess Lomecel-B benefits for AF via change versus placebo in the six-minute walk test(6MWT), to assess the dose-response relationship, and to evaluate bioactivity via changes in blood-based biomarkers. Enrolled subjects were aged 70\u201385 years with mild-to-moderate AF, a reduced 6MWT of 200-400m, and Tumor Necrosis Factor-\u03b1 of \u2265 2.5pg\/mL indicative of inflammaging. In total, 143 subjects received a single intravenous infusion of Lomecel-B at doses of 2.5 x 107 cells (25M, N=35), 5.0 x 107 cells (50M, N=30), 1.0 x 108 cells (100M, N=33), or 2.0 x 108 cells (200M, N=16), or placebo (N=29). Safety and efficacy assessments were performed at 1, 3, 6, and 9 months post-infusion. Increases in 6MWT and decreases in serum levels of the blood-based biomarker Soluble-Tie-2 were observed at 9 months in the Lomecel-B groups versus placebo. Notably, both observations were seen in a dose dependent fashion with 200M showing the highest effect. Based on the findings, a next-phase trial is being developed to advance this clinical program and will be presented.<\/jats:p>","DOI":"10.1093\/geroni\/igac059.2121","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T18:21:17Z","timestamp":1671560477000},"page":"562-562","source":"Crossref","is-referenced-by-count":0,"title":["BLOOD-BASED BIOMARKER CHANGES IN A PHASE 2B TRIAL ASSESSING LOMECEL-B IN OLDER ADULTS WITH FRAILTY"],"prefix":"10.1093","volume":"6","author":[{"given":"Kevin","family":"Ramdas","sequence":"first","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danial","family":"Mehranfard","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Naioti","sequence":"additional","affiliation":[{"name":"Longeveron, Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoff","family":"Green","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"McClain-Moss","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Gincel","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Hare","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Oliva","sequence":"additional","affiliation":[{"name":"Longeveron Inc. , Miami, Florida , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,20]]},"container-title":["Innovation in Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/innovateage\/article-pdf\/6\/Supplement_1\/562\/48310548\/igac059.2121.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/innovateage\/article-pdf\/6\/Supplement_1\/562\/48310548\/igac059.2121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T19:11:12Z","timestamp":1671649872000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/innovateage\/article\/6\/Supplement_1\/562\/6938469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":0,"journal-issue":{"issue":"Supplement_1","published-print":{"date-parts":[[2022,12,20]]}},"URL":"https:\/\/doi.org\/10.1093\/geroni\/igac059.2121","relation":{},"ISSN":["2399-5300"],"issn-type":[{"value":"2399-5300","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,11,1]]},"published":{"date-parts":[[2022,11,1]]}}}