14 DAY TRIAL // A collaboration of researchers coordinated by investigators at the Scripps Research Institute (SRI) recently uncovered a new approach to addressing brain inflammation. Their method does not cause the type of side-effects that drugs such as ibuprofen do.
The approach relies on blocking the action of a single enzyme, a metabolic pathway that appears to play an important role in controlling brain inflammation. Details of the study appear in a paper published in the October 20 issue of the journal Science Express.
According to the team, the purpose of this research was to find ways of combating the types of inflammation that can usually be treated with non-steroidal anti-inflammatory drugs (NSAID). This class of chemicals includes ibuprofen and aspirin, among many others.
Past investigations discovered that these types of inflammation are caused by a number of different enzymes, acting in different parts of the body. Most of the research was focused on the enzyme monoacylglycerol lipase (MAGL).
“Our findings open up the possibility of anti-inflammatory drugs that are more tissue-specific and don’t have NSAIDs’ side effects,” explains the chair of the Department of Chemical Physiology at SRI, Benjamin F. Cravatt. He was the senior author of the research paper.
The expert also holds an appointment as a member of the Skaggs Institute for Chemical Biology and the Dorris Neuroscience Center at the Institute. He and his team have been working on developing a drug that targets MAGL for the past few years.
Originally, they intended to have their chemical attack MAGL, which in turn was responsible for breaking down the pain-relieving protein called 2-AG. By reducing MAGL concentrations, the team hoped to allow 2-AG more wiggle room to dampen pain response.
“We noticed that the brains of the MAGL-inhibited mice showed reduced levels of arachidonic acid, a key precursor molecule for inflammatory lipids,” adds researcher Daniel Nomura. He explains that the new study is an offshoot of the original research.
Nomura is a former member of the Cravatt lab. He is currently an assistant professor at the University of California in Berkeley (UCB) Department of Nutritional Science & Toxicology.
“In both models, reducing MAGL – genetically or with our MAGL-inhibitor – provided the animals with protection from neuroinflammation. In principle, with a MAGL inhibitor we could avoid the gastrointestinal toxicity that’s associated with NSAIDs while still maintaining the anti-inflammatory effect,” Nomura concludes.