Scientists at Gladstone Institutes and SanBio have demonstrated that a stem cell therapy can restore normal brain activity patterns following a stroke in rats, even when administered a month after the event. This finding challenges the conventional wisdom that stroke treatments must be immediate to be effective.
Reversing Brain Hyperexcitability
The research, led by Jeanne Paz, PhD, at Gladstone, addresses the issue of brain hyperexcitability that often follows ischemic strokes. Ischemic strokes, which occur when blood flow to the brain is blocked, can cause brain cells to become overly active, leading to long-term problems like movement disorders and seizures. Paz and her team found that the stem cell therapy reversed this hyperexcitability, restoring balance in neural networks.
"This hyperexcitability has been linked to movement problems and seizures, but no therapies have been developed to effectively reverse it," said Paz, who is also an associate professor in the Department of Neurology at UC San Francisco.
SanBio's SB623 Cell Therapy
The stem cell therapy, utilizing modified human mesenchymal stem cells known as SB623, is under development by SanBio. In the study, rats were treated with these cells one month after experiencing a stroke. Subsequent measurements of brain activity revealed a restoration of balance in neural networks and an increase in proteins and cells crucial for brain function and repair.
Barbara Klein, PhD, a principal scientist at SanBio and first author of the study, noted, "It seems these cells are essentially jump-starting the brain’s own repair processes. This may open a new window of opportunity for the brain to recover, even in the chronic phase after a stroke."
Molecular Changes and Lasting Effects
Further analysis of blood samples from the rats revealed that the stem cell therapy normalized a specific combination of molecules involved in inflammation and brain health, which had been altered by the stroke. Despite the fact that fewer than 1% of the transplanted cells remained in the rats' brains a week after transplantation, the beneficial effects persisted.
"These effects were so striking that we repeated the experiments over and over because we didn’t quite believe them," said Paz. "It’s incredible that you can inject something short-lived into the brain and have lasting effects—not only on brain hyperexcitability, but also in the rest of the body."
Implications for Stroke Treatment
The study suggests that treatments administered even one month after a stroke can restore normal brain excitability, offering hope for patients with chronic brain injuries who currently have limited treatment options. Agnieszka Ciesielska, PhD, a postdoctoral researcher in Paz’s lab, emphasized the potential for new treatments for chronic brain injury patients.
SB623 cells have already been approved in Japan for improving chronic motor paralysis following traumatic brain injury, and SanBio is seeking approval from the US Food and Drug Administration for stroke and other indications.
