Keck School studies possible stroke recovery
New research from a USC team has possible implications for patients of neurological conditions including stroke, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and traumatic brain injury.
The research, published on April 2 in The Journal of Neuroscience, demonstrated that human neural progenitor cells, which build neurons (brain cells), can be prompted into action by a genetically engineered variant of a key protein in the body. A treatment developed using this variant could mean a stroke victim with irreversible brain damage might, days after suffering the stroke, be able to build new brain cells and regain cognitive and other functions thought to be lost forever.
“This implication is very exciting,” said Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. “We could be talking about a treatment that could be given within three days of a stroke, and then after a week, the patient could receive treatment weekly for several months to stimulate neurogenesis. When we give mice the variant two weeks after they suffer a stroke, we’ve seen good results and behavior.”
The research also described the molecular mechanism and pathway needed for neuronal production, Zlokovic said.
The variant, called 3K3A-APC, was developed by Zlokovic and colleagues at ZZ Biotech, a Houston-based biotechnology company he co-founded with USC benefactor Selim Zilkha. Genetically engineered 3K3A-APC is a variant of the naturally occurring protein APC, which plays a role in protecting the brain against bleeding and inflammation.
A study published in July by a team led by Zlokovic demonstrated that 3K3A-APC, given in tandem with tPA — also known as the “clot buster drug” and given to stroke patients shortly after they suffer a stroke — can counteract the sometimes dangerous bleeding conferred by tPA and improve cognitive function after a stroke. The difficulty for most patients is that tPA must be administered within three hours of a stroke; administered later, patients can suffer traumatic bleeding in the brain and a breakdown of the brain’s protective barrier.
In the new study, Zlokovic and colleagues analyzed how 3K3A-APC works in human neural progenitor cells. After stimulating the cells, the researchers observed that the cells differentiated mainly into neurons and suppressed differentiation into astroglial or oligodendroglial cells, which inhibit replenishment of neurons.
Future research will focus on whether 3K3A-APC may have applications for helping patients with neurological conditions other than stroke, Zlokovic said.
Funding was provided by the National Heart, Lung and Blood Institute of the National Institutes of Health (grant number HL63290).
The research team included scientists from ZZ Biotech; the Center for Neurodegenerative and Vascular Brain Disorders in the Department of Neurosurgery and the Center for Translational Neuromedicine in the Department of Neurology at the University of Rochester Medical Center; the Department of Medical Pharmacology and Blood Brain Barrier Research Laboratory at the University of Arizona; and the Department of Molecular and Experimental Medicine at The Scripps Research Institute.