"Capsaicin is the equivalent of trying to put out a house fire with a low-pressure garden hose," said Andrew Mannes, M. D., a scientist with NIH's Clinical Center, who is involved in RTX's clinical development. "RTX acts like a high-pressure fire hose. Just as the heavy blast of water from the fire hose can extinguish the flames, the heavy influx of calcium that RTX causes overwhelms the specific nerve cells that carry painful sensations and kills them."
Because nerve cells in the peripheral nervous system must first route their sensory signals to the spine, where they then are processed and sent onward to the brain, Iadarola's finding raised an intriguing therapeutic scenario: The cell bodies of these peripheral neurons bundle together in groups near the spine. If RTX were applied intrathecally and directly to the bundles, called dorsal root ganglia, the scientists believed that they could selectively kill specific neurons that express large amounts of the VR1 protein on their surface. By doing this, they also could turn off permanently certain painful sensations, such as noxious heat and certain inflammatory signals that can be involved in severe arthritis, peripheral neuromas, trigeminal neuralgia, and advanced cancer.
The research baton soon passed to NIH's National Institute on Drug Abuse to perform the needed toxicology studies on the intrathecal administration of RTX. Once completed, staff at the NIH Clinical Center painstakingly formulated RTX and produced the needed supply of the drug for NIH's current early-phase clinical study. The investigation is co-supported by NIDCR and NINDS.
"In recent years, NIH scientists have worked to enhance pain research and promote collaboration in the field," said NINDS Director Story Landis, Ph.D. "The unique scientific collaboration of five NIH components leading up to today's announcement has created an opportunity to develop a compound that might one day benefit patients."
"As the nation's medical research agency, NIH has tremendous capability to bring potential drugs to this developmental point," said NIDCR Director Martha Somerman, D.D.S., Ph.D. "We partner with industry to pull in their strengths and further study the drug. I'm happy that a partnership is in place for RTX now to test its potential to help those with intractable pain."
Source: NIH/National Institute of Dental and Craniofacial Research