In a multidisciplinary collaboration, Virginia Commonwealth University researchers are investigating a new strategy aimed at not merely halting cardiovascular disease, but actually reversing it.
Hu Yang, Ph.D., Qimonda Professor in VCU College of Engineering’s Department of Chemical and Life Science Engineering, and Shobha Ghosh, Ph.D., professor and associate chair for research in VCU School of Medicine’s VCU Department of Internal Medicine, are testing a nanomedicine drug delivery system to target certain cells in the artery wall that can lead to heart attack and stroke.
The underlying cause of cardiovascular disease is atherosclerosis, a condition that occurs when cholesterol or lipid-laden macrophage foam cells accumulate in the artery wall and form plaque. Ghosh and Yang have received a four-year, $2.54 million, multiple principal investigator grant from the National Heart, Lung, and Blood Institute at the National Institutes of Health to investigate using nanomedicine to facilitate the removal of cholesterol from the plaque — and eventually, the body — thereby regressing the existing plaque and decreasing the risk of acute cardiovascular events.
Ghosh, who is a Fellow of the American Heart Association, said atherosclerosis begins in the teen years. While all adults carry some level of plaque, many never go on to develop clinical symptoms later in adulthood — “but some of us will.” Treatment strategies such as taking cholesterol-lowering medications or aspirin “prevent further progression of the disease, but no medications are currently available to reduce the existing disease.”
The researchers want to find out what can be done to prevent plaque from rupturing and creating clots that can cause disruption of blood flow to the heart (a heart attack) or brain (a stroke). They also hope to identify a safe method of sending medication directly to the site of the plaque to remove the cholesterol and reverse the disease. “Regression is like a holy grail for cardiology,” Ghosh said.
As part of this quest, Yang said, “We developed a very innovative therapeutic delivery strategy by incorporating Dr. Shobha Ghosh’s findings. We can target plaque directly and promote the removal of lipids from the existing plaque.”
In 2014, Ghosh and Yang received a Multi-School Research Award from the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research for their project, followed by a VCU Quest Commercialization Fund Award in 2018.
Yang works to selectively deliver drugs to an intended target site using nanofibers based on dendrimers, a unique class of macromolecules with a well-defined globular structure and a large number of surface groups for functionalization.
“I have nearly 20 years of experience using dendrimers for drug and gene delivery,” he said. “I am still fascinated with the idea of using dendrimers to build new functional biomaterials and exploring their biomedical applications.” For atherosclerosis, “We use this as a platform to deliver the therapeutics needed and we have shown very impressive regression so far.”
Through the VCU Innovation Gateway, Ghosh and Yang have a patent pending on their technology, which is available for licensing to industry. Yang said they have generated interest “from pharmaceutical companies for commercialization opportunities.”
“We are at a very, very promising proof-of-concept stage,” Ghosh said.
Yang said he has enjoyed collaborating with Ghosh, who has made fundamental discoveries in liver gene therapy. Matthew Halquist, Ph.D., an assistant professor in the Department of Pharmaceutics in the VCU School of Pharmacy, and an expert in bioanalytical analysis, is also working on the project.
“We are teaming up to translate those fundamental discoveries, if possible, into clinical applications,” Yang said. “We’re working towards that goal.”