Field of Expertise
Ion Channel Pharmacology
Expertise
The goal of the proposed project is to develop a proprietary cream formulation of resiniferatoxin (RTX) nanoparticles to treat pain associated with diabetic peripheral neuropathy (DPN). We have investigated the mechanisms underlying DPN and found that Transient Recepor Potential Vanilloid 1 (TRPV1) expression and function are enhanced in sensory nerve terminals using animal models of painful DPN. Therefore, TRPV1 could be targeted for a novel treatment strategies. In fact, I was involved in the evaluation of a potent TRPV1 antagonist (GRC 6211) using electrophysiological experiments. Unfortunately, TRPV1 antagonists induced hyperthermia in clinical trials restricting their use. However, TRPV1 agonists could be considered to treat painful conditions by virtue of their ability to cause calcium influx leading to nerve terminal depletion/ablation. We have been working on RTX, a potent agonist of TRPV1 for the past 15 years. Our studies have revealed unique characteristics, which include high potency (full activation at femtomolar range), induces depolarization block preventing pain transmission in the short-term, and temporary nerve terminal depletion/ablation in the longer-term. These characteristics or RTX are unique and cannot be compared to any other agonist that I have studied, which is the basis of my patent. We take advantage of these unique properties to formulate a cream of RTX nanoparticles, which will be effective in neuropathic pain conditions including painful DPN. I have the expertise, leadership and motivation necessary to successfully carry out the proposed work. I have a broad background in cell biology, electrophysiology, and I have developed significant expertise in whole animal behavioral models. I have served as a permanent member of NTRC study section from 2006-2010 and involved as an ad hoc reviewer totaling 27 NIH grant panels over the past 20 years. I am on the Editorial Board of several peer reviewed journals. I have successfully trained graduate, undergraduate students, and postdoctoral fellows towards academic and industry careers. My laboratory has the infrastructure to conduct experiments from molecular level to whole animal level. We have also the necessary capability to extend our translational reach to human subjects in collaboration with the clinicians at various institutions (see attached letters). I have successfully administered NIH-funded projects, collaborated with other researchers, and produced several peer-reviewed publications. The current application builds logically on my expertise on animal models of pain and TRP channels and has culminated in the development of a cream formulation targeting TRPV1 to treat painful conditions.