{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:29:25Z","timestamp":1789385365462,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Stroke remains a leading cause of death and disability, underscoring the urgent need for treatments that enhance recovery. GDF11 (growth differentiation factor 11), a member of the TGF-\u03b2 (transforming growth factor-\u03b2) superfamily, is a circulating protein involved in cellular development and tissue repair. GDF11 has gained attention for its potential regenerative properties in aging and disease contexts, making it a candidate for stroke recovery therapies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>The therapeutic benefits of rGDF11 (recombinant GDF11) were evaluated using a rat ischemic stroke model, in which focal cerebral infarcts were induced in 8- to 10-week-old young adult male Sprague-Dawley rats by permanently occluding the proximal right middle cerebral artery. Rats received single or multiple doses of rGDF11 (0.1\u20134 mg\/kg) or vehicle from 24 to 72 hours post-injury. Sensorimotor functions were evaluated, and brain and serum samples were examined to determine the mechanisms of action and identify biomarkers, using immunofluorescence, target-specific ELISAs, and an aptamer-based proteomics platform.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>We confirmed rGDF11 activity in vitro and in established in vivo mouse models of cardiac hypertrophy and glucose metabolism and assessed the efficacy of rGDF11 treatment in 6 preclinical stroke studies using independent Contract Research Organizations, with all study animals and treatment groups blinded. All 6 studies revealed consistent improvement in sensorimotor outcomes with rGDF11. rGDF11-treated rats showed increased cortical vascularization and radial glia in the ventricular zone. Serum analysis revealed that rGDF11 caused dose-dependent decreases in CRP (C-reactive protein) and identified novel pharmacodynamic biomarkers and pathways associated with potential mechanisms of action of rGDF11.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>These results demonstrate that systemically delivered rGDF11 enhances neovascularization, reduces inflammation, promotes neurogenesis, and improves sensorimotor function post-injury in a rat model of ischemic stroke. More importantly, these data define an optimized and clinically feasible rGDF11 dosing regimen for therapeutic development in ischemic stroke and identify a panel of candidate pharmacodynamic and mechanistic biomarkers to support clinical translation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.049908","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T03:00:12Z","timestamp":1738810812000},"page":"996-1009","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Recombinant GDF11 Promotes Recovery in a Rat Permanent Ischemia Model of Subacute Stroke"],"prefix":"10.1161","volume":"56","author":[{"given":"Ori S.","family":"Cohen","sequence":"first","affiliation":[{"name":"Elevian, Inc, Research and Development, Newton, MA (O.S.C., M.S., Y.W., T.D., P.-C.L., C.D., B.C., A.D., S.J., N.J.M., K.L.D., C.J.D., M.A., A.S.)."},{"name":"Alevian, Inc, Research and Development, Lexington, MA (O.S.C., A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Sinha","sequence":"additional","affiliation":[{"name":"Elevian, Inc, Research and Development, Newton, MA (O.S.C., M.S., Y.W., T.D., P.-C.L., C.D., B.C., A.D., S.J., N.J.M., K.L.D., C.J.D., M.A., A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5841-6557","authenticated-orcid":true,"given":"Yongting","family":"Wang","sequence":"additional","affiliation":[{"name":"Elevian, Inc, Research and Development, Newton, MA (O.S.C., M.S., Y.W., T.D., P.-C.L., C.D., B.C., A.D., S.J., N.J.M., K.L.D., C.J.D., M.A., A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3405-8847","authenticated-orcid":true,"given":"Tyler","family":"Daman","sequence":"additional","affiliation":[{"name":"Elevian, Inc, Research and Development, Newton, MA (O.S.C., M.S., Y.W., T.D., P.-C.L., C.D., B.C., 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