How three researchers’ work is moving toward clinical use
BUBBLING UP
In Agata Exner’s lab, researchers spend a lot of time blowing bubbles.
These, though, are nanobubbles—nanoparticles with gas at their core—each of which is about 2,000 times smaller than a single grain of salt. By stimulating the nanobubbles with sound waves, Exner’s team is working toward a specific goal: improving cancer detection and targeted therapy.
Their process: Load nanobubbles with therapeutics and send them toward a tumor or other point of delivery in the body, tracking the movement with ultra - sound imaging technology.When the bubbles arrive at their destination, researchers use ultrasound vibration to pop the nanobubbles, which, in turn, “releases the cargo”within the nanobubble directly where it’s needed most, rather than all over.
“The precision and control is very helpful,” said Exner, PhD, the Henry Wilson Payne Professor, director of Case Center for Imaging Research and vice chair of basic science research in the Department of Radiology.
Exner’s team has been funded for nanobubble research in four areas so far: ultrasound imaging of prostate cancer, drug delivery, gene delivery—a recent grant from Moderna aims to see how nanobubbles can transport mRNA—and cancer immunotherapy. With the last approach, there’s no delivery required; it’s simply popping bubbles in a tumor. “It seems the popping action actually creates an immune response and recruits immune cells into a tumor.”
Exner explained. “So we can enhance the effect of existing immunotherapies or we can use the bubbles as an immunotherapy by themselves.” As Exner and her colleagues continue their research—including hope - fully soon filing an investigational new drug application with the Federal Drug Administration—Exner is confident in its potential to help fight diseases such as Type 1 diabetes, and ovarian, breast and prostate cancer.
BRIGHT SOLUTIONS:
Already, Exner’s team has seen success in its partnership with Jim Basilion, PhD, professor of biomedical engineering. For decades, Basilion has worked on image-guided approaches to light up tumors, whether for targeted drug delivery—like with Exner’s team—or for more precise, effective surgeries.
“My theory early on was that some tumor cells likely have migrated away from the tumor and might not be accessible to standard imaging probes,” leading surgeons to leave cancerous tissue behind, Basilion explained. Further complicating the issue—and causing many cancer surgeries to fail, he said—is that it’s often difficult to distinguish between healthy and cancerous tissues during surgery.
Basilion’s solution: develop technology that ensures surgeons only see the image probe’s signal when cancer is detected.
Eighteen years since he first started working on the concept, his proprietary technology, Fluorescent Image Resection Enhancement (FIRE)—part of his startup, Akrotome Imaging—is nearing use in human clinical trials. This spring, surgeons at Leiden University Medical Center in the Netherlands are expected to remove cancerous breast tissue during surgery, then use FIRE to identify any remaining tumor tissue so they can extract it.
In another project, Basilion’s partner, Research Assistant Professor Xinning Wang, PhD, developed a ligand to bind to the biomarker known as PSMA, or prostate -specific membrane antigen. Now, their team has shown in animal models that combining photodynamic therapy through this ligand-boundPSMA with image -guided surgery can potentially lead to surgical cures. Basilion and colleagues are founding a startup to drive this technology into clinical trials.
“At this phase, you are really just at the base of Mt. Everest of what needs to get done,”Basilion said. “Still, it’s completely invigorating.”
RESTORING FUNCTION:
Jerry Silver, PhD, knows firsthand the time it takes to bring research to reality—and also the exhilaration that comes with it. The renowned professor of neurosciences made international headlines in 2015 for his work restoring and repairing rat models’ nervous systems following spinal cord injuries. Eight years later, a spinoff company, NervGen Pharma Corp., successfully completed phase 1 clinical trials in humans of Silver’s drug, NVG -291.
The therapeutic peptide targets mechanisms that interfere with nervous system repair, bringing about functional recovery in preclinical models of spinal cord injury, peripheral nerve injury, multiple sclerosis and stroke. NVG -291 now has moved on to phase 2A trials and was granted “Fast Track” designation by the Food and Drug Administration to accelerate drug development.
“Seeing the full translational potential of my lab’s research on restoring function after spinal cord injury is just incredible,” said Silver, who now serves as a scientific advisor to NervGen. “Indeed, moving our discoveries all the way from the ‘bench to the bedside’ is the ultimate achievement that I have dreamed about since we began our studies … over four decades ago.”
But even as his “life’s work” comes to fruition in human trials, Silver isn’t slowing: He and post - doctoral fellow Yihui Bi, MD, PhD, are working on a new combinatorial therapy to improve function after spinal cord injury.
The preliminary results, Silver said, show even greater promise than his previous groundbreaking work.