New pain drug being developed at University of Maryland could offer relief without addiction

Researchers at the University of Maryland, Baltimore have developed a new drug that promises a possible breakthrough by offering strong pain relief while lowering the risk of addiction.

The drug, a synthetic opioid called UMB425 for now, is in the early stages of development — years away from human testing — and some experts cautioned that a number of complications could prevent it from ever coming to market. But there are high hopes for the drug as the nation looks for solutions to the opioid addiction epidemic.

"It's one of the biggest health care crises we have in the United States right now," said Andrew Coop, a professor at the University of Maryland School of Pharmacy who is developing the drug. "There are people who suffer daily from the side effects of the opioid."

While opioids are generally effective for pain relief, they can lead to addiction as users become more tolerant of them and require larger doses.

Opioids work on the brain through their interaction with what are known as receptors, Coop said. There are three primary opioid receptors called mu, delta and kappa. Most opioids act on the mu receptor, causing pain relief as well as tolerance, dependence and feelings of euphoria.

UMB425 is unique in that it acts on both the mu receptor and the delta receptor. It's not clear why, but activating both at the same time reduces the side effects of tolerance and addiction, Coop said.

Past research established that taking a drug that acted on the mu receptor and another drug that acted on the delta receptor at the same time diminished those negative side effects, but Coop said his aim was to design a single drug to act on the two receptors.

Coop's team created UMB425 with the help of Alex MacKerell, director of the University of Maryland's Computer-Aided Drug Design Center. It has been under development for about 10 years. They published their research on in its ability to act on the two receptors in the journal ACS Chemical Neuroscience in 2013.

The drug's effect on multiple receptors is a "unique feature," said David Thomas, a health science administrator at the National Institute on Drug Abuse. He called the 2013 study "solid" and said it showed that the drug results in less tolerance developing over time.

Still, more research is needed.

"It's a promising finding, but it's very preliminary," Thomas said.

While Coop said it's as effective as the opioid morphine, the drug has been tested so far only on rodents. Coop said his team hopes to start testing the drug soon on primates and begin clinical human trials in about five years.

UMB425 still creates a euphoric high for the user, which Coop wants to find a way to eliminate to reduce any potential for abuse.

The National Institute on Drug Abuse estimated in 2012 that 2.1 million people nationwide were addicted to or abusing prescription opioid pain relievers. Another 467,000 people are addicted to heroin, a cheaper and more readily available alternative.

About 28,000 people died after overdosing on prescription pain relievers and heroin in 2014, the highest number on record, according to the Centers for Disease Control and Prevention.

About 100 million American adults suffer from chronic pain, the Institute of Medicine estimated in a landmark study in 2011. Prince, the renowned musician who died in April from an accidental overdose of the powerful painkiller fentanyl, was the latest high-profile death in the opioid addiction epidemic.

"The [U.S. Food and Drug Administration] has a clear mandate that we need new ways to treat pain," said Dr. David Maine, director of the Center for Interventional Pain Medicine at Mercy Medical Center. "They're not going to entertain anything that's the same old. … This is novel, it's exciting."

"It's clearly very promising," he added. "We know that there's pain-relieving potential there."

Drugs such as UMB425 generally face many obstacles to getting FDA approval, including the ability of patients to tolerate it, Maine said.

"The opioid epidemic is here and now; I hope by the time something like this comes on the market, that issue will be headed in the other direction," he said.

Besides the potential for addiction, opioids have a host of negative side effects that become more problematic as the patient develops tolerance and the dosage is increased. For example, too large a dose can depress breathing, which can lead to death.

If UMB425 doesn't cause tolerance in patients over time, doses won't need to be increased and the risk of other serious side effects, such as life-threatening constipation, will decrease, Coop said.

Patients also wouldn't experience painful withdrawal symptoms and wouldn't need to seek relief by taking even more opioids, he added.

"It would just be like taking any other drug," Coop said.

The National Institute on Drug Abuse's Thomas urged restraint in prematurely judging the new drug at this stage. "I wouldn't wave the flag and say, 'This is it — we've found the alternative to opiates,'" he said. "Whether this pans out or something else pans out is the question."

Thomas said he thinks the drug could be part of doctors' pain relief arsenal in the future, but he said many different new therapies could develop.

"We've been using opioids a lot for pain, and there's been a pretty profound impact to that many opioids being available to the American people," he said. "Opioids have their place in pain treatment, but they should be part of a more comprehensive pain treatment."

Coop said the drug had about $2 million in grant funding so far and that he needs another $2 million to get it to market.

"This approach could be a panacea; it's just not going to happen tomorrow," he said. "It needs significant investment."

Baltimore Health Commissioner Dr. Leana Wen, who considers UMB425 more as potentially "one tool in the toolbox" to fighting opioid addiction, suggested an easier and more practical way to have an impact on the opioid addiction epidemic.

"Certainly advances in science can be helpful," she said. "But there is a larger problem of overprescribing opioids. ... There is a culture of a pill for every pain, a quick-fix culture that doctors and patients have to change."

cwells@baltsun.com

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