Stroke is the leading cause of disability in the U.S., with over 800,000 new stroke patients every year. New treatment strategies are needed to maintain the patients’ quality of life after the stroke. Therefore, researchers have come up with a new gene therapy that converts glial cells, the abundant support cell in the brain, into neurons, repairing the damage that results by stoke and significantly improving function.
According to the lead author Yuchen Chen, the current treatment for stroke has a narrow time window, typically within a few hours after the occurrence of stroke. Many patients cannot receive the treatment in time and as a result, often suffer from permanent disability caused by irreversible neural loss.
The human brain consists of approximately 86 billion neurons. While mini-strokes can be tolerated, moderate stroke involving the loss of billions of neurons leaves harsh effects that do not spontaneously recover.
Glial Cells to Neurons.
Yuchen Chen and his team discovered a new approach to regenerate functional neurons by using glial cells, a group of cells surrounding every single neuron in the brain that provide the required support to neurons. Glial cells can divide and regenerate themselves, especially after brain injury.
The team previously reported that a single genetic neural factor, NeuroD1, could convert glial cells into functional neurons inside mice brains who had Alzheimer’s disease, but the total number of neurons generated was limited. The team believed that this limited regeneration was because of the retroviral system used to deliver NeuroD1 to the brain.
In the current study, the team used AAV viral system, which is the first choice for gene therapy in the nervous system, to deliver NeuroD1 into the mouse motor cortex which has suffered from a stroke.
Several neurons die after stroke but surviving glial cells can accumulate and form a glial scar in the stoke areas. The AAV system is designed to introduce NeuroD1 in the glial cells, turning them directly into neuronal cells. The technology has not only increased neural density in the stroke areas but also significantly reduced brain tissue damage caused by strokes. Additionally, the converted neurons show similar properties to the neurons that were lost after a stroke.
The researchers also found that this direct conversion technology can rescue cognitive functional deficits induced by stroke. The study provides a proof-of-concept that glial cells in the brain can be called as the fountain of youth to regenerate functional new neurons for brain repair for stroke and many other neurological disorders that result in neuronal loss.
“Our next step is to further test this technology and ultimately to translate it into clinically effective therapies to benefit millions of patients worldwide,” said Chen.