Gary K Steinberg1, Douglas Kondziolka2, Lawrence R Wechsler2, L Dade Lunsford2, Maria L Coburn2, Julia B Billigen2, Anthony S Kim2, Jeremiah N Johnson2, Damien Bates2, Bill King2, Casey Case2, Michael McGrogan2, Ernest W Yankee2, Neil E Schwartz2. 1. From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.). cerebral@stanford.edu. 2. From the Department of Neurosurgery (G.K.S., M.L.C., J.N.J.) and Department of Neurology and Neurological Sciences (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurosurgery, New York University and NYU Langone Medical Center, NY (D.K.); Department of Neurosurgery (L.D.L.) and Department of Neurology (L.R.W., J.B.B.), University of Pittsburgh Medical School and University of Pittsburgh Medical Center, PA; Department of Neurology, University of California, San Francisco (A.S.K.); SanBio, Inc, Mountain View, CA (D.B., C.C., M.M., E.W.Y.); and Western Statistical Consulting, LLC, Phoenix, AZ (B.K.).
Abstract
BACKGROUND AND PURPOSE: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. METHODS: Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow-derived mesenchymal stem cells (SB623). RESULTS: All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5-10.3; P<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, -2.7 to -1.3; P<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4-27.0; P<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6-18.2; P<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (P<0.001 for European Stroke Scale). CONCLUSIONS: In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936.
BACKGROUND AND PURPOSE: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. METHODS: Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow-derived mesenchymal stem cells (SB623). RESULTS: All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5-10.3; P<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, -2.7 to -1.3; P<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4-27.0; P<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6-18.2; P<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (P<0.001 for European Stroke Scale). CONCLUSIONS: In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936.
Authors: S S Rabinovich; V I Seledtsov; N V Banul; O V Poveshchenko; V V Senyukov; S V Astrakov; D M Samarin; V Ya Taraban Journal: Bull Exp Biol Med Date: 2005-01 Impact factor: 0.804
Authors: Bruce C V Campbell; Peter J Mitchell; Timothy J Kleinig; Helen M Dewey; Leonid Churilov; Nawaf Yassi; Bernard Yan; Richard J Dowling; Mark W Parsons; Thomas J Oxley; Teddy Y Wu; Mark Brooks; Marion A Simpson; Ferdinand Miteff; Christopher R Levi; Martin Krause; Timothy J Harrington; Kenneth C Faulder; Brendan S Steinfort; Miriam Priglinger; Timothy Ang; Rebecca Scroop; P Alan Barber; Ben McGuinness; Tissa Wijeratne; Thanh G Phan; Winston Chong; Ronil V Chandra; Christopher F Bladin; Monica Badve; Henry Rice; Laetitia de Villiers; Henry Ma; Patricia M Desmond; Geoffrey A Donnan; Stephen M Davis Journal: N Engl J Med Date: 2015-02-11 Impact factor: 91.245
Authors: H Isaac Chen; Dennis Jgamadze; James Lim; Kobina Mensah-Brown; John A Wolf; Jason A Mills; Douglas H Smith Journal: Tissue Eng Part A Date: 2019-03-29 Impact factor: 3.845
Authors: Giorgio Battista Boncoraglio; Michela Ranieri; Anna Bersano; Eugenio A Parati; Cinzia Del Giovane Journal: Cochrane Database Syst Rev Date: 2019-05-05
Authors: Paul M George; Byeongtaek Oh; Ruby Dewi; Thuy Hua; Lei Cai; Alexa Levinson; Xibin Liang; Brad A Krajina; Tonya M Bliss; Sarah C Heilshorn; Gary K Steinberg Journal: Biomaterials Date: 2018-06-14 Impact factor: 12.479