Lighting Up Nerves to Scale back Surgical Hurt

Unintended nerve injury remains a common and debilitating complication of surgery, contributing significantly to long-term morbidity despite advances in technique and imaging. Illuminare-1 is a novel imaging agent that binds specifically to a nerve sheath component called myelin and fluoresces under blue light, allowing nerves to be seen clearly against surrounding tissue during surgery. The agent’s first-in-human Phase 1 trial showed rapid onset and sustained nerve visualization, paving the way for broader clinical evaluation.

In this Innovation Spotlight, Stewart McCallum, the chief medical officer of Illuminare Biotechnologies, discusses the need for better visualization agents and the current and future promise of Illuminare-1.

How common is nerve damage during surgery, and what consequences do patients face?

Iatrogenic nerve injury is, unfortunately, a persistent and pervasive complication in modern surgery. Despite significant advancements in surgical technique, including the widespread adoption of robotic platforms and optical field magnification, nerve damage remains a leading cause of short- and long-term morbidity. We estimate the overall incidence of iatrogenic nerve injury ranges between 1.5 and 15 percent across various surgeries, placing over 10 million patients at risk annually.‎^1-2

The consequences for patients can be catastrophic and life-altering.^3-5 In radical prostatectomy, for instance, damage to the dorsal or cavernosal nerves can lead to erectile dysfunction in 30-50 percent of men and urinary incontinence in 20-44 percent. In head and neck surgeries such as thyroidectomies, damage to the recurrent laryngeal nerve can cause paralysis or loss of voice. We see similar risks in breast reconstruction, where 20-60 percent of patients report loss of sensation and/or chronic pain, and in hernia repairs, where chronic pain affects a significant percentage of patients. These injuries don’t just affect physical function; they have profound impacts on long-term quality of life and mental health.

What are the limitations of current visualization agents?

The primary limitation is the specificity of current visualization techniques, which generally rely on white light and cause nerves to look remarkably similar to surrounding fascia and connective tissue. Even experienced surgeons can struggle to differentiate them; one study showed that expert observers disagreed more than 20 percent of the time on whether a structure was a nerve under white light.⁶

Existing agents, such as indocyanine green (ICG), are valuable for visualizing blood flow (angiography) or lymphatics, but they do not target nerves. They rely on perfusion or nonspecific uptake, which doesn’t help distinguish nerve fiber from a nearby small blood vessel. Other nerve-specific agents in development often have limitations such as slow onset of action, requiring dosing hours before surgery, or complex administration protocols that disrupt the operating room’s workflow. Others are prohibitively expensive. Surgeons need a cost-effective solution that provides immediate, high-contrast confirmation of nerve tissue in real time.

What is Illuminare-1, and how does it work in the operating room?

Illuminare-1 (rizedisben) is a proprietary small-molecule fluorophore designed to solve the above problem. Its mechanism of action is unique: it binds directly to myelin, which is found in the protein sheath that insulates nerves. All motor, sensory, and autonomic nerves contain myelin to varying degrees. This direct binding allows us to “light up” the nerve structure itself, rather than just the fluid around it.

In the operating room, Illuminare-1 is designed for seamless integration. The agent is administered intravenously just 30 minutes before the surgeon needs to visualize the nerves. It has a rapid onset of action, becoming visible within minutes, and provides a durable fluorescent signal that lasts for well over 3 hours, covering the critical dissection phases of most complex surgeries. When the surgeon switches their standard laparoscopic or robotic camera to blue-light mode (wavelength 370-425 nm), nerves fluoresce brightly against the surrounding background, creating a clear visual map. We have successfully visualized nerves as small as 64 microns in diameter—less than a human hair—using this technology. It fits perfectly into the existing workflow without requiring new, expensive capital equipment for hospitals already equipped with standard fluorescence imaging systems for minimally invasive surgeries and robotic surgeries. For open surgeries, surgical loupes equipped with a blue headlamp in addition to the standard white light can be used to achieve the same effect.

How was your first in-human study set up, and what did you see?

Our Phase 1 trial was a single-arm, open-label, dose-escalation study conducted at Memorial Sloan Kettering Cancer Center. We enrolled 38 patients undergoing robotic-assisted radical prostatectomy. The primary goals were to assess safety and identify a clinically effective dose for nerve visualization.

The results were incredibly encouraging.⁷ At our optimal dose of 3.0 mg/kg, we achieved 100 percent sustained visualization of the obturator nerve, a key motor nerve in the pelvis, which served as a reference nerve for the study. More importantly, we successfully visualized the delicate neurovascular bundles in 89 percent of patients at this dose. These bundles are microscopic structures, and they are critical for normal erectile function. Seeing them light up so clearly, distinct from the prostate capsule and surrounding tissue, validated our preclinical work. We also observed a very promising safety profile: out of 38 patients we had only one grade 2 adverse event—a rash on a patient with a history of allergic responses to bandages—possibly related to the drug, and one transient grade 2 episode of photosensitivity that was deemed likely drug-related.

What does the ability to visualize nerves in real time mean for patients?

It means precision and preservation. By making invisible nerves visible, we empower surgeons to make better intraoperative decisions. Instead of estimating where a nerve bundle lies based on anatomical landmarks, they can see exactly where it is. This allows for more confident dissection, reducing the risk of accidental cutting, stretching, or thermal injury from cautery.

For patients, this translates directly to better functional outcomes. In prostatectomy, it means a higher chance of preserving sexual function and urinary continence, which are key attributes that men consider when deciding to undergo a radical prostatectomy. For women undergoing a unilateral or bilateral mastectomy, it could mean preserving sensation and avoiding chronic pain from neuromas. Again, these are substantial factors that they will live with for the rest of their lives. In head and neck surgery, it means protecting voice and facial movement. Ultimately, it’s about reducing the devastating complications that undermine a patient’s quality of life after they’ve been “cured” of their primary condition, which is most commonly cancer.

Your first in-human study was in radical prostatectomy patients. Where else could this agent be effective?

The mechanism of Illuminare-1 is widely applicable because it targets myelin, which is present in all nerves throughout the body. While prostatectomy was an ideal initial proof-of-concept due to the complexity of pelvic anatomy and the proximity of the neurovascular bundles to the prostate capsule, the potential applications are vast.

Our next focus is on breast reconstruction postmastectomy, where nerve preservation is becoming a new standard of care to reduce or prevent numbness and chronic pain postoperatively. We also see significant potential in head and neck surgery, such as thyroidectomy and parotidectomy, to protect facial and laryngeal nerves, as well as in hernia repair to avoid injury to sensory nerves that can cause chronic groin pain. Orthopedic surgeries, such as spinal fusion and hand surgery, are other areas where nerve identification is critical. Essentially, any procedure where nerves are at risk is a potential application for Illuminare-1.

What’s next for Illuminare Biotechnologies?

We are moving rapidly to build on our Phase 1 success. We are planning to initiate Phase 2 clinical trials in the first half of 2026. These studies will focus on nerve-sparing breast reconstruction. These trials will further validate efficacy across different surgical modalities and anatomical regions.

From a corporate perspective, we are currently raising our Series B financing to fund these trials and propel us toward a Phase 3 pivotal study. We are targeting a New Drug Application filing by 2028. We are also actively engaging with strategic partners in the MedTech space—companies that produce surgical robotics and imaging systems—who view enhanced visualization as a key differentiator for their platforms. Our goal is to make Illuminare-1 a standard of care in operating rooms worldwide, transforming nerve preservation from an anatomical guess into a visual certainty. As the invited commentators who reviewed our published results in JAMA Surgery put it, “the future of surgery is lit!”