TSRI Researchers Develop Assay to Help Identify New Pain Medication Candidates JUPITER, FL August 23, 2017 Scientists at the Scripps Research Institute (TSRI) in Jupiter, Florida, have developed a test that will help scientists identify new drug candidates for treating pain that have fewer side effects, like addiction. The study conducted by scientists in Scott Hansen's lab at TSRI was recently published in Cell Reports.
Neurological drugs, like painkillers, are notoriously messy. They bind to targets throughout the brain and produce myriad undesirable side effects. One reason for this is that the tests, or assays, that researchers use to identify how molecules interact with certain receptors have been difficult to apply to ion channels, a type of structure that drives brain function. The Hansen Lab has overcome this limitation by developing an assay that will allow scientists to screen an ion channel, TREK-1, that is known to be involved in pain.
Ion channels are proteins situated in the membrane of a cell. When they open, they allow ions to flow into or out of the cell, altering the cell's electrical charge and, ultimately, its behavior. While most scientists agree that lipids inside the cell's membrane have important roles in the cell's function, the interactions between lipids and ion channels have been difficult to study due to a lack of applicable assays.
There's this mystery about membranes and lipids, said Scott Hansen, associate professor of molecular medicine at TSRI. We've known that they are important regulators and potential targets [for drugs], and there just really wasnt an assay to screen them at the level needed.
In order to conduct a high-throughput assay, scientists need to isolate the channels by solubilizing the environments surrounding them. Ion channels are found in the lipid membrane, which unfortunately is not soluble. Hansen explained that they're like a clump of fat that won't go down the sink when you're trying to do your dishes.
Fortunately, Hansen and his team realized that like fat, once the lipid membrane could be broken up and solubilized with a little detergent, the channel could be used in a soluble assay. The team used the strategy in this study to show that a lipid called PIP2, which was thought to agonize the channel, is actually antagonizing or blocking it.
Next, the assay will be advanced to drug discovery and used to screen for possible drug candidates that will act on the receptor and may be useful in managing pain. TSRI is known for its pharmaceutical-grade drug-screening capabilities, and the technique is likely to be applicable for screening other ion channels.
In addition, the study provided evidence that these channels can be opened and closed by lipids, like PIP2. Scientists have long known that some ion channels are controlled by neurotransmitters binding to the membrane structure (ligand-gated ion channels). Hansen and his team have recently proposed one more way these channels are controlled. Lipids, which float throughout the lipid membrane itself, can bind to the receptors and cause them to open or close as well. Hansen calls these channels lipid-gated ion channels. This aspect of ion channel function opens a whole new set of questions about how our brains work.
In addition to Hansen, three other researchers worked on the study: Lead Researcher Cerrone Cabanos of TSRI, as well as Miao Wang and Xianlin Han of the Sanford Burnham Prebys Medical Discovery Institute in Orlando, Florida.
The work was supported by an NIH Director's New Innovator Award (1DP2NS087943-01 to S.B.H.).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.
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For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8118
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TSRI Researchers Develop Assay to Help Identify New Pain Medication Candidates JUPITER, FL August 23, 2017 Scientists at the Scripps Research Institute (TSRI) in Jupiter, Florida, have developed a test that will help scientists identify new drug candidates for treating pain that have fewer side effects, like addiction. The study conducted by scientists in Scott Hansen's lab at TSRI was recently published in Cell Reports.
