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Hyunsuk Shim, Ph.D. |
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| Dennis Liotta, Ph.D. |
A Chinese vine called “Walk Seven Steps and Die” and “Intestine Breaking Plant” sounds more like poison than cure. But it is, in fact, both.
Emory University scientists are finding new ways to turn triptolide, an extract from this plant, into safe treatments for rheumatoid arthritis, inflammation, and inflammatory bowel disease. Chemist Dennis Liotta, biologist Hyunsuk Shim, and colleagues are tweaking the chemistry of this deadly herbal extract and testing it successfully in mouse models of inflammatory disease.
"The chemists pick apart the molecule—keeping the parts that are helpful and excising everything else," says Liotta. They also test changes in solubility and toxicity, hoping to reach a place where it can be tested for safety in humans.
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T. Wilfordii Plant |
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Chemical Structure of Triptolide |
“We have come up with some formulations that are potent but not very toxic,” says Liotta. “We are still playing with some structural variations in the molecule to find the best pharmacologic profile. These are relatively simple molecules, and we have lots of options in how we can vary their structure. The results have been extremely promising.”
Work on triptolide has been ongoing at Emory for about eight years. Earlier, other researchers isolated the active compound of triptolide. “We are currently developing new ‘analogs’ by manipulating triptolide’s chemical structure to generate a potent compound that plays a key role in regulating genes involved in inflammation as well as cancer,” Shim says.
When administered to mice, these analogs have safely and successfully treated inflammation. Emory already has issued patents for some of these triptolide analogs and also has several patents pending in the United States, Europe, Australia, Canada, and Japan.
What distinguishes Emory’s triptolide patents is the positive biological data from the mouse disease models. In a mouse paw inflammation model, modified triptolide visibly reduced swelling and reduced measurements of inflammatory cytokines. Mouse inflammatory bowel disease was also successfully treated with triptolide analogs.
Emory’s initial product application is aimed toward rheumatoid arthritis treatment, in a market similar to the drug Celebrex. Continued work on triptolide could lead to powerful new drugs for diseases involving autoimmune and inflammatory processes, including cancer, heart disease, and even depression.
“Emory is actively engaged in discussions with external industry experts to solicit early feedback and identify individuals to help develop a business model for this opportunity,” says Jennifer Moore, a molecular physiologist and licensing associate at Emory’s Office of Technology Transfer.
Liotta is optimistic. The drug discovery process is one fraught with risk, trial and error, and brutal years of work that could easily go up in smoke—the half-life could prove too short in animals, or it might be metabolized too quickly to take effect. But Emory’s analogs of triptolide show great promise.
“In this game, it can all fall apart,” he says. “When we make some small molecules, we push them as far as we can until they break. So far this one hasn’t broken.”
Techid: 00033 |
