For the past few years, researchers have been running a trial of a first generation stem cell therapy for stroke patients. This used stem cell lines cultured from donors rather than from the patients. As is the case for some other forms of cell therapy, the resulting benefits appear linked to reduced inflammation rather than any other effects of the transplanted cells. Otherwise, the effects on patients were not as large as hoped would be achieved via this type of approach.
A trial looking at whether a single dose of millions of adult, bone-marrow-derived stem cells can aid stroke recovery indicates it’s safe and well-tolerated by patients but may not significantly improve their recovery within the first three months. However, the trial does provide evidence that giving the therapy early – within the first 36 hours after stroke symptoms surface – may enhance physical recovery by reducing destructive inflammation as well as the risk for serious infections and that these benefits might continue to surface many months down the road. “There is solid evidence from our basic science work and now some indicators from this phase 2 patient trial that giving these stem cells can safely help dial back the body’s immune response to stroke injury that can ultimately further damage the brain and body.”
The study at 33 centers in the United States and the United Kingdom from October 2011 to December 2015 included 129 adults with moderately severe strokes. A dose of 400 million cells were given to a handful of patients to establish safety, the dose was then increased to 1,200 million cells for the majority of patients. About half of patients received a single dose of the stem cells while the remainder received placebo. Patients in both arms were able to also have received standard stroke therapies. While the study made several adjustments along the way to enable better enrollment, it was an early adjustment in the timeframe for giving the therapy that may have impacted results. Trial leaders extended the timeframe for therapy from the original 24 to 36 hours – which was suggested by previous animal studies – to 24 to 48 hours. That adjustment was in response to limited hours at some centers to thaw and otherwise prepare the cells for patients as they qualified for the study. Now cell developers have reduced thaw times from 6 hours to 30 minutes and made the process much easier, which should enable tighter timeframes for giving the treatment moving forward.
Although the primary analysis of results was done at 90 days, about 80 percent of study participants were followed for a full year. It was those longer-term results, particularly in the small number of patients who got therapy early, that suggested the cell therapy group might be more likely to continue to recover, with reduced disability and fewer infections one year out than the placebo group. The multipotent cells, dubbed MultiStem, were developed by the international biotechnology company Athersys Inc., which also funded the clinical trial. Doses given in the study were the largest ever given in a human cell therapy trial.
Researchers who have studied the cells believe they primarily work by modulating the body’s immune response, which can go a bit haywire following a stroke. An immune response is definitely needed to help the brain heal and to remove debris generated by dead or damaged tissue. But there also may be a secondary response that includes immune organs like the spleen, beginning to shrink in size within the first hours after symptoms of stroke. “Some inflammation is good, but in a big stroke, it almost always overshoots. We think this secondary neuroinflammatory process is preventing the natural healing tendencies of the body. We think cell therapy prevents this early egress of cells from the spleen that go to the brain and, by doing that, they also prevent the later exhaustion of the spleen and immune system.”