SB623 is a proprietary, cell-based investigational product made from modified and cultured adult bone marrow-derived mesenchymal stem cells that undergo temporary genetic modification. Implantation of SB623 cells into injured nerve tissue in the brain is expected to trigger the brain's natural regenerative ability to recover lost motor functions.
STEMTRA was a 12-month, Phase 2, randomized, double-blind, surgical sham-controlled, global trial evaluating the efficacy and safety of SB623 compared to sham surgery in patients with stable chronic neurological motor deficits secondary to TBI. In this study, SB623 cells were implanted directly around the site of brain injury.
To be eligible for this trial, patients (ages 18-75) had to be at least 12 months post-TBI and had a Glasgow Outcome Scale extended (GOS-E) score of 3-6 (e.g., moderate or severe disability). Patients must also had to be able to undergo all planned neurological assessments and have had no seizures in the prior three months. The primary endpoint was mean change from baseline in Fugl-Meyer Motor Scale (FMMS) score which was used to measure changes in motor impairment at six months after treatment with SB623 cells. The STEMTRA trial enrolled 61 patients from 13 surgical and 18 assessment sites in the U.S., Japan and Ukraine.
In this study, SB623 met its primary endpoint, with patients treated with SB623 achieving an average 8.3 point improvement from baseline in the FMMS, versus 2.3 in the control group, at 24 weeks (p=0.040). Of patients treated with SB623, 18 (39.1%) reached a 10 or more point improvement of FMMS compared to one control patient (6.7%; p=0.039). No new safety signals were identified. The most commonly reported adverse event were headaches.
Aizman I, Tate CC, McGrogan M, Case CC.
J Neurosci Res. 2009 Nov 1;87(14):3198-206. doi: 10.1002/jnr.22146.
Yasuhara T, Matsukawa N, Hara K, Maki M, Ali MM, Yu SJ, Bae E, Yu G, Xu L, McGrogan M, Bankiewicz K, Case C, Borlongan CV.
Stem Cells Dev. 2009 Dec;18(10):1501-14. doi: 10.1089/scd.2009.0011.
Glavaski-Joksimovic A, Virag T, Chang QA, West NC, Mangatu TA, McGrogan M, Dugich-Djordjevic M, Bohn MC.
Cell Transplant. 2009, 18(7):801-14. doi: 10.3727/096368909X470801. Epub 2009 Sep 28.
Tate CC, Fonck C, McGrogan M, Case CC.
Cell Transplant. 2010,19(8):973-84. doi: 10.3727/096368910X494885. Epub 2010 Mar 26.
Glavaski-Joksimovic A, Virag T, Mangatu TA, McGrogan M, Wang XS, Bohn MC.
J Neurosci Res. 2010 Sep;88(12):2669-81. doi: 10.1002/jnr.22435.
Dao MA, Tate CC, Aizman I, McGrogan M, Case CC.
J Neuroinflammation. 2011 Oct 7;8:133. doi: 10.1186/1742-2094-8-133.
Mesenchymal Stromal Cells to Treat Brain Injury
Tate CC and Case CC
Chapter in "Neurological Disorders", InTech, 2012
Transplanted Mesenchymal Stem Cells Aid the Injured Brain through Trophic Support Mechanisms
Tate CC and Case CC
Chapter in "Stem Cells and Cancer Stem Cells, Vol 4", M.A. Hayat (Ed), 2012
Tajiri N, Kaneko Y, Shinozuka K, Ishikawa H, Yankee E, McGrogan M, Case CC, Cesar V. Borlongan CV
PLoS ONE 2013 Sep 4;8(9): e74857. doi: 10.1371/journal.pone.0074857. eCollection 2013
Harvey A, Yen TY, Aizman I, Tate C, Case C
PLoS ONE 2013 Nov 14;8(11): e79283. doi: 10.1371/journal.pone.0079283. eCollection 2013
Dao M, Tate CC, McGrogan M, Case CC.
J Transl Med. 2013 Mar 27;11:81. doi: 10.1186/1479-5876-11-81
Aizman I, McGrogan M, Case CC.
Stem Cells Transl Med. 2013 Mar;2(3):223-32. doi: 10.5966/sctm.2012-0119. Epub 2013 Feb 19.
Dao MA, Nolta JA, and Case CC
Advances in Neuroimmune Biology 2013, 4:177-185. doi: 10.3233/NIB-130064
Aizman I, Tirumalashetty BJ, McGrogan M, Case CC.
Stem Cell Res Ther. 2014 Feb 26;5(1):29. doi: 10.1186/scrt418.
Tajiri N, Duncan K, Antoine A, Pabon M, Acosta SA, de la Pena I, Hernadez-Ontiveros DG, Shinozuka K, Ishikawa H, Kaneko Y, Yankee E, McGrogan M, Case C, Borlongan CV.
Front Syst Neurosci. 2014 Jun 24;8:116. doi: 10.3389/fnsys.2014.00116. eCollection 2014
Aizman I, Vinodkumar D, McGrogan M, Bates D.
Stem Cells Dev. 2015 Jul 15;24(14):1623-34. doi: 10.1089/scd.2015.0083. Epub 2015 May 20.
Tate CC, Chou VP, Campos C, Moalem AS, Di Monte DA, McGrogan M, Case CC, Manning-Bog AB.
J Tissue Eng Regen Med. 2015 Oct 6. doi: 10.1002/term.2081. Epub ahead of print
Steinberg GK, Kondziolka D, Bates D; SB623 Stroke Phase 1/2A Study Group.
Stroke. 2016 Dec;47(12):e269. Epub 2016 Nov 15. doi: 10.1161/STROKEAHA.116.015209
Aizman I, Holland WS, Yang C, Bates D.
Cell Med. 2016 Oct 6;8(3):79-85. doi: 10.3727/215517916X693357. eCollection 2016 Dec 3.
Steinberg GK, Kondziolka D, Wechsler LR, Lunsford LD, Coburn ML, Billigen JB, Kim AS, Johnson JN, Bates D, King B, Case C, McGrogan M, Yankee EW, Schwartz NE.
Stroke. 2016 Jul;47(7):1817-24. doi: 10.1161/STROKEAHA.116.012995. Epub 2016 Jun 2.
