UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

(Press-News.org) When surgeons dissect tissue to remove a tumor or make a repair they must work cautiously, relying on electrophysical monitors and their own anatomical knowledge to avoid cutting nerves, which could complicate the patient’s recovery.

A University of New Mexico surgeon has helped develop and test a first-of-its-kind drug that binds to nerve tissue and fluoresces – emits light – enabling surgeons to better see the nerves they’re trying to work around.

A newly published study in Nature Communications reported that bevonescein – a short chain of amino acids attached to a fluorescing molecule – was safe to use highlighted longer stretches of nerves than would be visible to the naked eye, improving the odds of operating without causing injury.

“The way that I explain this drug to patients is that I think if we can help surgeons see things better, they can do faster, more efficient, safer surgery,” said Ryan Orosco, MD, an associate professor and otolaryngologist (head and neck surgeon) in the UNM School of Medicine who co-authored the paper.

The journal article reported on a small Phase 1-2 study of the drug, which was tested on 27 cancer patients to evaluate its safety and efficacy. “The trial was for patients having a neck dissection to remove lymph nodes or a parotid surgery or a thyroid surgery,” he said. “In all of those cases, there are cranial nerves that are important to identify, work around and protect.”

A larger Phase 3 study currently underway includes patients at UNM Hospital and is expected to be completed by this summer, Orosco said. It will assess whether use of the imaging agent meaningfully improves overall surgical outcomes, something the initial trial was not designed to determine.

Orosco’s involvement in the development of the drug dates back to his ENT residency at the University of California, San Diego, where he spent a year-long research fellowship in the lab of Quyen Nguyen, MD, PhD. She had worked closely with the late biochemist Roger Tsien, PhD, who won the Nobel Prize in 2008 for discovering green fluorescent protein, enabling the development of methods to “tag” specific molecules and tissue types, such as cancer cells.

Nguyen’s research eventually led to the development of bevonescein, and Orosco, who went on to do a head and neck cancer fellowship at Stanford before joining the UCSD faculty, played a role in developing the clinical trial protocol and performed many of the surgeries in the study.

He joined the UNM faculty in late 2022 and now serves as the national principal investigator for the Phase 3 trial of the drug, which now includes 10 sites.

Patients in the trials receive an IV infusion of the drug prior to surgery, but it is quickly cleared by the kidneys, Orosco said. “We can image them five, six, seven, eight hours later, and it still stays bound to the nerves, but it flushes out of the body within 12 hours.”

In the operating room, surgeons use microscopes with special lights and filters that illuminate the surgical site at a specific frequency that causes the drug to fluoresce. The nerves appear as wormlike yellowish-green structures that thread through the surrounding tissue.

An upcoming phase of the research will evaluate the use of specially modified headband-mounted magnifying loops of the sort that surgeons wear, rather than the microscope. “Testing those loops in a spinoff trial is a critical and practical step toward real-world implementation,” Orosco said.

If the Phase 3 trial shows clear clinical benefit from the use of bevonescein during head and neck surgery it could win FDA approval, leading to wider use in surgical procedure throughout the body. “Once the FDA has approved it for a certain indication, then it'll be on the shelves,” he said. “Surgeons can also use it off-label for whatever they want. Then the big question is, how does that go? Who starts using it and in which types of surgeries?”

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