Modified Stem-Cell Implants Improve Function in Chronic Traumatic Brain Injury
In the phase 2 STEMTRA (NCT02416492) double-blind, multinational clinical trial, participants with chronic motor deficits from traumatic brain injury (TBI) treated with modified, bone-marrow derived, mesenchymal stem cells (n=46) (SB623; SanBio Group, Mountain View, CA) vs a sham surgery (n=15), had improved motor function.
Participants treated with modified stem cells vs sham had an 8.3±1.4- vs 2.3±2.5-point improvement (P=.04) from baseline on the Fugl-Meyer Motor Scale (FMMS) 24 weeks after treatment. Those who received the middle dose of 5x106 cells vs sham had statistically significant improvement on FMMS at 24 (P=.002) and 48 weeks (P=.02). Improved upper and lower extremity function and quality of life were observed with stem-cell therapy vs sham, although the study was not powered to detect statistically significant change in these measures.
Peter McAllister, MD, medical director and chief medical officer, New England Center for Neurology and Headache and study investigator noted, “People with chronic losses of function from TBI have few to no effective treatments. We saw individual participants regain motor skills, including fine motor hand use and speech, as well as statistically significant improvements in motor function with stem-cell vs sham treatment. These data show the potential for SB623 to provide clinically meaningful improvement to people with chronic TBI, and we look forward to continuing its development."
The stem-cell treatment uses mesenchymal, bone-marrow derived stem cells from a single donor, transfected with the cell-signaling gene NOTCH1 and grown in culture. Stem cells were delivered to a brain lesion, observable with neuroimaging, on the contralateral side of the motor deficits via a 3-mm burr hole. Participants who were randomly assigned to sham surgery, had the same procedure without cell delivery. All participants had their usual physiotherapy ceased during a lead-in period and received standardized physiotherapy after their procedure consisting of hand exercises, stand/squat exercises, and walking to be done twice daily for the first 24 weeks of the study.
Adults, age 18 to 75, who had motor deficits secondary to a TBI that occurred 12 or months earlier, with moderate-to-severe motor disability, no seizures in the prior 3 months, and at least 2 scores under 33 on the Require Motricity Index 10-81 (UE Scale) and/or 10-78 (LE Scale) with both positive and at least 1 less than 25.
At 48 weeks, no participants discontinued the study for any reason. All participants had at least 1 adverse event and these were evenly balanced across all 4 arms of the study. No correlation between dose and adverse events was observed and no dose-limiting toxicities occurred.
The study results were presented at the American Academy of Neurology (AAN) Annual Meeting on April 5, 2022, in Seattle, WA.