Researchers in the Center for Nanotechnology in Drug Delivery at the UNC Eshelman School of Pharmacy have received a translational NIH grant worth $783,000 over two years to develop a way to deliver to the brain a protein capable of repairing some of the damage caused by stroke.
The grant from the National Institute of Neurological Disorders and Stroke will fund the CNDD’s efforts to design a new nanoparticle delivery system capable of transporting a protein called brain-derived neurotrophic factor to the brain and central nervous system. BDNF is a protein that supports the survival of and growth of certain neurons in the brain, particularly those in areas related to learning, memory and higher thinking.
Alexander “Sasha” Kabanov, Ph.D., Dr.Sci., is the principal investigator on the grant. He is the director of the CNDD and the Mescal S. Ferguson Distinguished Professor at the School’s Division of Molecular Pharmaceutics. He said that BDNF shows the potential to protect and regenerate neurons when administered after stroke. However, the use of BDNF as therapeutic agent is hindered by the difficulty of delivering it in meaningful amounts to the brain.
“We propose to create a novel, biocompatible nanoformulation of BDNF, which has shown to increase brain delivery of active BDNF and enhance its beneficial effect on poststroke neurological recovery in animal models,” Kabanov said. “Our hope is that we can identify a lead drug candidate that can be taken forward into further preclinical development as a treatment for the effects of ischemic stroke.”
Ischemic stroke accounts for 87 percent of all stroke and is caused by an obstruction — usually a blood clot — in the vessels supplying blood to the brain, according to the American Stroke Association. Stroke is the fifth-leading cause of death and disability in United States.
Kabanov’s team will produce and encapsulate BDNF in shells made of polyethylene glycol and poly-L-glutamate that are less than 100 nanometers in size.
“Preliminary studies suggest that nano-BDNF will strongly improve the brain uptake of BDNF and increase efficacy of BDNF treatment to elicit neuroprotection and neuro-restoration after stroke,” he said.
Kabanov is collaborating with William Banks, M.D., an expert in neurovascular biology and protein transport to the brain, and Louise McCullough, M.D., Ph.D., a neuro-oncologist and expert in cerebral vascular disease. Banks is the associate director of research at the Geriatric Research Education and Clinical Center of the Veterans Affairs Puget Sound Health Care System and a professor at the University of Washington School of Medicine in Seattle. McCullough is chair of the Department of Neurology at the University of Texas Medical School at Houston.
The project title is “Nanoformulation of the BDNF for Treatment of Stroke,” NIH grant number 1R21NS088152-01A1.