Introduction: No treatment exists to restore lost brain function after stroke. Animal studies demonstrate that brain transplantation of SB623, a human bone marrow derived stromal cell with transient transfection of Notch-1 gene, after experimental stroke can improve neurologic outcome. This clinical study is the first North American trial of intraparenchymal transplantation of bone marrow derived cell therapy for chronic stroke patients.
Methods: This is a two center (Stanford University and the University of Pittsburgh) open label safety and dose escalation feasibility study. Stereotactic transplantation is targeted to the subcortical peri-infarct area. Inclusion criteria include 18–75 yo, 6–60 mos post subcortical MCA ischemic stroke, mRS 3–4 and NIHSS > 7. Safety endpoints include WHO toxicity scale, MRIs and clinical follow-up to 2 years. The primary efficacy endpoint is European Stroke Scale (ESS) at 6 mos; secondary efficacy measures are ESS, NIHSS, Fugl-Meyer, mRS, cognitive scores up to 2 years, and FDG-PET at 6 months.
Results: Eighteen patients have been treated (6 with 2.5M cells, 6 with 5M and 6 with 10M). Follow-up is currently 6 mos in 12 pts, 9 mos in 9 pts and 12 mos in 6 pts. There were 3 serious adverse events related to the surgery, but not to the cells (seizure, subdural hematoma, pneumonia). Cytokine levels, HLA antibody levels, and PBMC function did not change from baseline. Three measures of efficacy (NIHSS, ESS, Fugl-Meyer) all show a trend toward improvement. Since the sample size is small, no statistical analysis has been done. Two patients showed remarkable improvement in their motor (2) and language function (1) within 24 h of surgery, effects which have been sustained during follow-up (12 and 3 mos). These were the only 2 patients with new FLAIR lesions (DWI neg) in the motor cortex that resolved at 2 mos.
Conclusions: Intraparenchymal transplantation of human modified bone marrow derived stromal cells in chronic stroke patients is safe, feasible, and shows a trend toward neurologic improvement. Larger studies will be initiated to further assess clinical efficacy.
Patient Care: It has the potential to restore lost brain function in chronic stroke patients for whom no treatment currently exists.
Learning Objectives: To understand 1) the early safety and efficacy results from a phase 1/2A study of intraparenchymal cellular therapy for chronic stroke patients and 2) the potential of intraparenchymal transplantation of human bone marrow derived stromal cells to restore lost brain function in chronic stroke patients.