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August 22, 2016
Animal study examines method for restoring brain cells killed by stroke or other neurological diseases.
Scientists and clinicians have long dreamed of helping the injured brain repair itself by creating new neurons, and an innovative NIH-funded study published today in Nature Medicine may bring this goal much closer to reality. A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage.
The therapy relies on the combination of two methods that show promise as treatments for stroke-induced neurological injury. The first consists of surgically grafting human neural stem cells into the damaged area, where they mature into neurons and other brain cells. The second involves administering a compound called 3K3A-APC, which the scientists have shown helps neural stem cells grown in a petri dish develop into neurons. However, it was unclear what effect the molecule, derived from a human protein called activated protein-C (APC), would have in live animals.
A month after their strokes, mice that had received both the stem cells and 3K3A-APC performed significantly better on tests of motor and sensory functions compared to mice that received neither or only one of the treatments. In addition, many more of the stem cells survived and matured into neurons in the mice given 3K3A-APC.
“This USC-led animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke,” added Jim Koenig, Ph.D., a program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which funded the research. “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”
The researchers induced stroke-like brain damage in mice by disrupting blood flow to a specific part of their brains. One week later – the equivalent of several months in humans – the team inserted the stem cells next to the dead tissue and then gave the mice several infusions of either a placebo or 3K3A-APC.
“When you give these mice 3K3A-APC, it works much better than stem cells alone,” said Berislav Zlokovic, M.D., Ph.D., the University of Southern California professor who led the research. “We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host’s nervous system.”
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