A new compound in development at the University of Minnesota shows promise as a breakthrough drug for treating chronic pain.
The new compound, developed by Philip Portoghese, Ph.D., of the University of Minnesota’s College of Pharmacy, appears to be the first of its kind. A patent has been applied for, and the University’s Center for Translational Medicine has been conducting proof-of-concept studies. As a potential medication, the compound offers benefits lacked by current medications: It does not induce the body to develop tolerance or dependence, as opioid painkillers do. It is more potent than other opioid pain medications. It reduces and inhibits neuropathic pain, post-operative pain, burn pain, spinal injury pain and inflammation.
Close to 31 percent of adults in the U.S. have experienced chronic pain1 at an economic cost of about 600 billion dollars annually.2 Chronic inflammatory pain, such as that which occurs with cancer and diabetic neuropathy, is especially difficult to treat over the long haul.
Portoghese’s compound, called MMG22, represents a novel approach to chronic pain. It decreases the activity of nerve signals involved in pain production and the activity of those involved in inflammation.
The body contains many types of cells involved in sending signals throughout the nervous system. Opioid receptors, a part of the body’s system of pain relief, respond to compounds produced by the body as well as opioid drugs such as morphine. Glutamate receptors serve a number of functions, but are involved in the process of inflammatory pain.
“The problem all along is that we’ve been looking at these receptors very simplistically,” explains Portoghese, adding that current drugs work on one receptor or another, not both. “We have accumulating evidence that different receptors associate with one another. You have to take that into account when developing a drug, because that association changes the signaling pathways.”
Observing that receptors involved in pain relief in the spine often work in combination with those that are involved in inflammation, Portoghese set out to deal with both receptors simultaneously. “The drug was designed by attaching two molecules. One molecule blocks the effects of the glutamate receptors. Meanwhile, the other molecule activates the opioid receptors.” This means that the new compound helps reduce signals that result in hypersensitivity to pain while decreasing the activity of neurons that mediate pain. “This makes a very potent analgesic because you are decreasing inflammation while making the patient less sensitive to pain,” says Portoghese.
In tests with laboratory animals, the compound has been quite effective in very small doses. Moreover, it appears not to produce negative side effects, such as tolerance, that reduce the impact of opioid medications over time.
The University’s Center for Translational Medicine (CTM) helps investigators like Portoghese ready a potentially beneficial therapy for clinical evaluation and development. Robert Schumacher, Ph.D., its scientific director, says that in this case, CTM has conducted initial studies verifying Portoghese’s findings and exploring ways the drug, if developed, might be administered. Should the compound appear viable for greater development, CTM will help advance it through Phase I clinical trials and bring the compound to the attention of companies that might license it for development into a medication. “The long term goal,” says Schumacher, “is the development of technologies that will benefit patients.”
And working towards this same goal, the university’s Office for Technology Commercialization is in the process of identifying and engaging potential commercial partners for Portoghese’s technology. OTC will be presenting this opportunity at the upcoming BIO Convention, a global biotechnology partnering event in San Diego later this month. Raj Udupa and Karen Ohlfest from OTC will be marketing Portoghese’s technology to both pharmaceutical and biotechnology companies at BIO with the ultimate goal of identifying a partner that can translate Portoghese’s discovery to a drug that can truly transform patient lives.
1 Johannes, CB, Le TK, Zhou X, Johsnton JA, and Dworkin RH. “The prevalence of chronic pain in United States adults: results of an Internet-based survey.” Journal of Pain, 2010 Nov;11(11):1230-9.
2 American Pain Society Media Backgrounder, March 2014. http://www.americanpainsociety.org/about-aps/Press-Room/about-aps-press-room.html
Post by Vincent Hyman, a freelance writer based in St. Paul, Minn.