Elena Batrakova, Ph.D., is principal investigator on a new R01 grant from the National Institute of Neurological Disorders and Stroke to explore cell-based gene delivery to the brain as a therapy for Parkinson’s disease. The grant is worth up to $1.7 million over five years.
Batrakova and her team at the UNC Eshelman School of Pharmacy’s Center for Nanotechnology in Drug Delivery will genetically modify white blood cells called monocytes to produce glial cell–derived neurotrophic factor, or GDNF, and deliver it to the brain. Glial cells provide support and protection for nerve cells throughout the brain and body, and GDNF can heal and stimulate the growth of damaged neurons.
Parkinson’s affects more than a million people in the United States, and up to 60,000 new cases are diagnosed each year. One of the defining characteristics of Parkinson’s is the loss of neurons in the brain that produce dopamine, a critically important neurotransmitter responsible for a variety of functions in the body. Current therapy for Parkinson’s does not treat the disease but only manages the symptoms.
“Currently, there are no treatments that can halt or reverse the course of Parkinson’s disease. There are only therapies to address quality of life, such as dopamine replacement,” Batrakova said. “However, studies have shown that delivering neurotrophic factor to the brain not only promotes the survival of neurons but also reverses the progression of Parkinson’s disease.”
The presence of the blood-brain barrier — a filtration system that tightly regulates what is allowed to pass from the bloodstream into the brain — has long been an impediment to treating Parkinson’s and other neurodegenerative disorders with medication. The barrier blocks many relatively small drug molecules from getting through; large molecules such as GDNF and similar proteins stand no chance of passing without help.
Enter white blood cells. The specialized cells of the immune system, including monocytes, macrophages, and T cells, can easily penetrate the blood-brain barrier and move rapidly to sites of brain inflammation and degeneration.
In previous experiments, Batrakova was able to load white blood cells with bits of DNA called plasmids that allow the cells to produce therapeutic proteins like GDNF and transfer genes to sites of inflammation in the brain. Batrakova’s studies have shown that delivering neurotrophic proteins to the brain not only promotes the survival of neurons but also reverses the progression of Parkinson’s disease. Preliminary studies in mouse models of Parkinson’s treated with engineered white blood cells and GDNF showed decreased brain inflammation, significant neuroprotection and improved motor functions.
With the NINDS grant, Batrakova with further study the mechanisms that allow white blood cells to effectively transfer genetic material. In addition to white blood cells, she will also explore the use of induced neural stem cells as a delivery system. Induced neural stem cells can be created from a patient’s skin or other cells and have shown promise in therapeutic areas such as cancer treatment.
Batrakova is an associate professor in the Division of Molecular Pharmaceutics and Pharmacoengineering.