Abstract 149: A Novel Phase 1/2A Study of Intraparenchymal Transplantation of Human Modified Bone Marrow Derived Cells in Patients with Stable Ischemic Stroke
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: Seventeen patients have been treated (6 with 2.5M cells, 6 with 5M and 5 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.
Author Disclosures: G.K. Steinberg: None. D. Kondziolka: Research Grant; Significant; SanBio, Inc. N.E. Schwartz: None. L. Wechsler: Ownership Interest; Modest; NeuroInterventional Therapeutics. Consultant/Advisory Board; Modest; Lundbeck: Abbott Vascular. Other; Modest; DSMB - DIAS 3/4; Steering Committee - ACT I. L.D. Lunsford: Ownership Interest; Significant; b Elekta. Consultant/Advisory Board; Significant; b Elekta. M.L. Coburn: Research Grant; Significant; SanBio, Inc. J.B. Billigen: Research Grant; Significant; SanBio, Inc. H. Keren-Gill: Research Grant; Significant; SanBio, Inc. M. McGrogan: Employment; Significant; SanBio, Inc.. Consultant/Advisory Board; Modest; Stanford University. C. Case: Employment; Significant; SanBio, Inc. K. Mori: Employment; Significant; SanBio, Inc. Ownership Interest; Significant; SanBio, Inc. E.W. Yankee: Employment; Significant; SanBio, Inc.. Ownership Interest; Significant; SanBio, Inc.
- © 2014 by American Heart Association, Inc.