Ultra High-Throughput Drug Screen for Lipid-Regulated Ion Channels
Abstract
Objective: This application seeks to develop a novel platform for developing medications for pain, in particular, chronic pain. We outline a method to identify pain medication that target pain without side effects. In Aim 1, we develop assays or ways to monitor drugs binding to molecules that control pain. Importantly our methods are suitable for identifying a candidate medication out of millions of possible compounds. In a second aim, we validate our screening method and compare selectivity to previous methods that were inadequate for identifying highly specific medications. Problem: The lack of selectivity drugs for the determinants of pain limits our understanding of pain and the ability to treat pain. Our best pain medications come from natural products such as opioid plants and toxins from snails. But current medications are limited and/or have unwanted side effects. Nerves control pain. The switches that set the threshold for pain (ion channels) are known, but the switches for controlling pain thresholds are very similar to the thresholds that control heartbeat and mood. Furthermore, these electrical switches are imbedded in lipids (the oily part of the nerve), greatly hampering drug discovery. The pharmaceutical industry has known the problems for a long time, but to date hasn’t overcome the hurdles and we continue to lack good pain medications. Benefits to Service Members and Veterans: War Veterans are susceptible to chronic pain due to traumatic injuries sustained in battle and the physical demands of being a Soldier. Strategies to greatly accelerate the drug discovery process could reduce the time required to make better pain medication. Prescription pain medications have created a drug epidemic in the United States. Better pain medications without side effects are needed. The military uses anesthesia extensively in both combat and civilian settings. Understanding the mechanism of inhaled anesthetics is the first step in reducing the risks associated with their use. In theory, a waking compound could be developed based on an understanding of the mechanism of action. This would minimize the number of skilled medical personnel required to perform a surgery, decrease the military personnel in harm’s way, increase the feasibility of surgery in combat, and decrease the time to treatment after injury. Many anesthetic drugs used in combination with inhaled anesthetics are also drugs with the potential for abuse (opioids and barbiturates, benzodiazepine). Understanding the mechanism of inhaled anesthetics will likely lead to a better understanding of the related anesthetics and their synergistic effects with inhaled anesthetics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810782
Entities
People
- Scott B. Hansen
Organizations
- Scripps Research
- United States Army