Cell Therapy for Chronic TBI

Abstract

ObjectiveTo determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).MethodsThis 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15).ResultsThe primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI: 0.3–11.8); p = 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25).ConclusionsSB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls.Classification of evidenceThis study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

Clinical results of neurorestorative cell therapies and therapeutic indications according to cellular bio-proprieties

“…The scores of intracerebral stereotactic implantation of modified bone marrow-derived MSCs (SB623) for chronic traumatic brain injury (TBI) were not statistically significant compared with the control group in the functional scales, which included Disability Rating Scale (DRS), Action Research Arm Test (ARAT), gait velocity (GV), T scores of NeuroQOL upper and lower extremity domains and Global Rating of Perceived Change assessed by patient and clinician, although the treated patients significantly exhibited reduction in motor impairment (FMMS) scale scores [ 109 ]. A randomized, double-blind, placebo-controlled trial of MSC secreting neurotrophic factor cells for ALS showed similar slope change of Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in treated and placebo participants [ 110 ].…”

Cell-Based Therapies for the Treatment of Traumatic Brain Injury: Promises and Trajectories

“…To date, several clinical trials (NIH-registered and non-NIH registered) have attested to the safety of stem cell administration for TBI. Importantly, those trials have investigated different routes of administration such as intravenous [55], intracerebral [53], intraventricular [74], and intrathecal injections [75]. Similarly, they reported on various cell types such as allogeneic and autologous bone marrow-derived mesenchymal and mononuclear cells, as well as umbilical cord-derived mesenchymal stem cells [53,55,72,75].…”

“…Importantly, those trials have investigated different routes of administration such as intravenous [55], intracerebral [53], intraventricular [74], and intrathecal injections [75]. Similarly, they reported on various cell types such as allogeneic and autologous bone marrow-derived mesenchymal and mononuclear cells, as well as umbilical cord-derived mesenchymal stem cells [53,55,72,75]. However, in most instances, the study period was limited to one year and longer follow-ups are required.…”

Present and future avenues of cell‐based therapy for brain injury: The enteric nervous system as a potential cell source

“…In another neuropathological disease close from stroke, traumatic brain injury, a multicenter trial STEMTRA demonstrated the safety and Class I efficiency of the same mesenchymal SB623 cells. Motor status was improved ( n = 61 patients) [82]. Motor recovery was also improved after intravenous graft of autologous MSCs and fMRI activation, used as a fMRI biomarker, was enhanced in the primary motor cortex in grafted patients ( n = 31 patients) [83].…”