Nervelight™, a topical, intraoperative nerve imaging agent that is selective for at-risk nerve tissue in cancer resections

We have shown in vivo Proof-of-Concept of Nervelight™, a nerve imaging agent that is comprised of a commercially available Near InfraRed (NIR) dye in the 800 range attached to recombinant human Nerve Growth Factor (800-rhNGF). When Nervelight™ was applied topically, intra-operatively in an incision model of just-euthanized naïve rats, we showed selective uptake into cavernous nerves (below), facial nerves (below), and sciatic nerve (data not given). When studied recently in live animals, the selectivity and brightness of Nervelight™ is further enhanced. We will update this page when additional data is publicly available.

It is well established that rhNGF has a high affinity for tropomyosin kinase A (TrkA) receptors which are expressed on the distal ends of peripheral nerves. Our results confirm that the main mechanism underlying the selectivity of Nervelight™ is its binding to TrkA receptors that are exposed after incision. Of note: since rat neuroanatomy involving binding of NGF to TrkA is highly homologous in humans, these results are clinically predictive. In parallel, we have prototyped a “repurposed rhNGF” that we expect can be substituted for the research-grade material now currently used.

Intravitreal implants with FA-rhBDNF: optic neuritis, indirect Traumatic Optic Neuropathy (iTON)

Optic neuritis involves inflammation of the optic nerve, usually accompanied by pain in one eye. Although it may resolve without treatment, the Standard of Care is high-dose, systemic glucocorticoids. About half of cases presage multiple sclerosis in about two years. Separately, indirect Traumatic Optic Neuropathy (iTON) is a condition that affects our Troops, our Wounded Warriors and our Veterans, almost always after they have been exposed to blast or chemical trauma. Recently, the Rex lab at Vanderbilt University Medical Center (Bernardo-Colón et al., 2019) showed that inflammation of the optic nerve is one of the first pathologies to result from blast trauma. We have shown Proof-of-Concept of drug delivery of small molecules to the optic nerve. We attached a commercially available Near InfraRed (NIR) dye in the 800 region to recombinant human brain-derived neurotrophic factor (800-rhBDNF, Benlight™). In two studies, when injected intravitreally or intracisternally, 800-rhBDNF appeared to reach the optic nerve heads in the posterior of the eye, in the retinal layer that connects the optic nerve to the eye.

Study #1: intravitreal 800-rhBDNF

This was a 2X2 study in which we tested intravitreal (IVT) and topical 800-rhBDNF and IVT and topical 800-rhNGF (unpublished data).

Study #2: intracisternal 800-rhBDNF

This study showed that when 800-rhBDNF is injected intracisternally in a single dose, midline at the base of the skull where the optic nerve originates, the NIR dye was localized to the optic nerve and transported to the optic nerve heads. Data were presented in a poster in collaboration with Absorption Systems (San Diego, CA) at Military Health System Research Symposium, August 2019. An excerpt from that poster is given below.

Anti-cancer conjugates: Optic Pathway Glioma, a rare form of neurofibromatosis (children’s cancer caused by genetic disease, NF1 and NF2)

(in development)

Aptamer-based device to detect beverage contamination (“date rape drug detector”)

(in development)

Non-opiate, pen-injectable to treat chronic pain

(in development)

In the zoster-induced model of allodynia, herpes zoster injected into the footpad creates pain near the spinal cord. We injected 4X once daily 5µg. Four injections reduced pain to baseline, an effect that had rapid onset and sustained duration for the two weeks of the study.

Inadequate treatment of pain is the single largest cost problem in the Veterans Administration and in the civilian population. Cost in the system to treat pain is driven largely by ineffective drugs, so that patients return to the physician repeatedly for re-evaluation and new combinations of various classes of drugs. In the civilian population pain is the most frequent reason that patients seek medical care, accounting for about 1.5% of all healthcare visits. (Taylor 2006) This is estimated to cost America about $100 billion in direct and $100 billion in indirect costs (Clark 2007).

The total cost of all treatment for Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF, in Afghanistan) returnees was estimated at $350 - $650 billion in 2007 (Clark 2007). Assuming 47% of OEF/OIF returnees seek treatment for pain, this suggests that the cost of treating their pain is $150 - $300 billion.

“... [I]t is expected that about 50% of all OIF/OEF servicemembers will eventually access VA healthcare”... of these, about half of OEF/OIF returnees (47%) will seek treatment for pain, and half of these will receive opiate therapy along with other, often CNS-active pain drugs. (Clark 2007). Of those being treated for pain, about 44% of injured troops receive some form of opiate therapy (Clark 2007). This level is consistent with historical use (Clark 2002).

White Paper

An historical review of selected functions of exogenous Nerve Growth Factor: selective binding, endocytosis, and axonal transport.

March 2024