E-News Exclusive
Interventional News
Gene Therapy via Ultrasound Could Offer New Tool in Fight Against Heart Disease and Cancer
Combining ultrasound energy and microbubbles to poke holes in cells may prove to be a new tool in the fight against cardiovascular disease and cancer, according to researchers from the University of Pittsburgh (Pitt) and University of Pittsburgh Medical Center (UPMC). A study on this gene therapy approach, called sonoporation, appears in the Proceedings of the National Academy of Sciences (PNAS).
“We can use ultrasound energy in combination with small, gas-filled bubbles to selectively open up cells to allow the delivery of therapeutic agents,” says Brandon Helfield, PhD, lead author of the study and a postdoctoral fellow at the Center for Ultrasound Molecular Imaging and Therapeutics at UPMC. “With a focused ultrasound beam, this approach lets us tune this delivery to the precise location of disease while sparing healthy tissue. Our study looks at some of the biophysics at play and helps us get closer to refining this technique as a clinical tool.”
Current approaches to gene therapy often use viruses to gain access inside cells; this can cause severe side effects, including inflammatory immune system reactions. To address this issue, researchers have developed gene-loaded intravascular microbubbles that can be targeted to release their payloads by direct navigation of focused ultrasound energy.
The Pitt researchers developed an ultrafast imaging camera—the only one of its kind in North America—capable of reaching speeds up to 25 million frames per second. Using the camera, these researchers examined the biophysics of sonoporation. They determined that the oscillating bubbles need to generate a minimum amount of localized shear stress, beyond which cell membranes perforate and allow entry of a targeted therapeutic.
“By allowing us to actually see the microbubbles vibrating at millions of times per second, our unique camera enabled us to determine that microbubble-induced shear stress is the critical factor for sonoporation,” says Xucai Chen, PhD, a research associate professor of medicine, Pitt Division of Cardiology, and Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, who codeveloped the camera system. “This new information, in turn, will facilitate the intelligent design of treatment protocols and microbubble fabrication to preferentially cause the desired effect of opening nearby cells. It also gives us a starting point to investigate how cells cope with this treatment.”
Researchers believe the findings will help them understand how the process of sonoporation works, as well as how experts can tailor the approach, including ultrasound amplitude levels and microbubble designs, toward its eventual clinical use.
“It’s critical for us to understand the biophysical mechanisms of sonoporation in order to translate this approach into an effective gene or drug delivery tool for patients,” says Flordeliza Villanueva, MD, a professor of medicine at Pitt, director of the Center for Ultrasound Molecular Imaging and Therapeutics, and the senior author of the investigation. “Building on the PNAS study, we are continuing to investigate how sonoporation affects the function of treated cells and to develop strategies to maximize its therapeutic effects.”
— Source: University of Pittsburgh Medical Center
Loyola Among First Centers to Offer Dissolving Cardiac Stent
Loyola Medicine will be among the first health systems in the country to offer heart patients a new stent that is absorbed by the body once it has served its purpose.
On July 5, the FDA approved Absorb, the first absorbable cardiac stent. Loyola was among the centers that participated in the pivotal clinical trial that led to the stent’s approval.
“This is the future,” says Fred Leya, MD, Loyola’s medical director of interventional cardiology. “The leave-nothing-behind philosophy will prevail.”
A traditional stent is a tube-shaped metal scaffold that serves the vital purpose of keeping a coronary artery open following a balloon angioplasty. But after two or three months, the stent is no longer needed because the artery has healed and can remain open on its own. Once this occurs, the stent does more harm than good.
A metal stent can cause inflammation inside the blood vessel; this creates scar tissue that can narrow the artery. Metal stents also can lead to the formation of blood clots that can block an artery and trigger a heart attack. Most metal stents are drug eluting, meaning they emit a drug that helps prevent the growth of scar tissue. This reduces, but does not eliminate, the risk of restenosis (renarrowing) of a coronary artery.
The Absorb stent remains intact until the artery has healed and no longer is in danger of collapsing. After serving its purpose, the stent gradually breaks down into carbon dioxide and water. The stent is made of the same synthetic polymer used to make absorbable sutures.
“I think patients will demand this device once they understand the limitations of metal stents,” Leya says.
More than two-thirds of patients who require stents will qualify for the Absorb stent. The device is not intended for use in arteries narrower than 2.5 mm.
— Source: Loyola University Health System
