SEARCH NEWS & VIEWS


Scientists Discover 'Outlier' Enzymes that Could Offer New Targets to Treat Diabetes, Inflammation
Perfecting a Viral Pack Mule
Facing an Opioid Epidemic
Team Awarded $3.4 Million to Develop Novel Treatments for Drug Addiction, Mood Disorders

NEWS & VIEWS HOME
PAST ISSUES
CAMPUS UPDATES
SCIENTIFIC CALENDAR
CA AUDITORIUM EVENTS
CONTACT




FOLLOW US

Facing an Opioid Epidemic

By Madeline McCurry-Schmidt

Kathy Schnur was excited to spend Christmas break with her only son.

After years of struggling with anxiety, depression and drug addiction, Schnur’s son Patrick was “ecstatic” to end his first semester with a 4.0 GPA in pharmacy school, and he planned to meet Schnur in San Francisco to celebrate.

“He said that was to be my Christmas present,” said Schnur.

But Patrick never boarded the plane, the airline told Schnur. When she called security at his dorm, they checked his room and found him dead from an apparent heroin overdose.

In the weeks since Patrick’s funeral, Schnur has been met with an outpouring of compassion—and many people shared their own stories of loved ones lost to overdose. “If this is what I have encountered just in the last few weeks, what is happening all over the country?” asked Schnur.

TSRI Researchers Develop Promising Treatment

The U.S. Centers for Disease Control and Prevention (CDC) calls heroin addiction an “epidemic”—noting that its use has increased across most age groups and all income levels in the last 20 years. In fact, the country has seen a 200 percent increase in overdose deaths involving opioids from 2000 to 2014.

Adding to the scourge is a synthetic heroin-like drug called fentanyl, a potent opioid often used as a substitute or mix-in with heroin. Over the years—to skirt U.S. Drug Enforcement Administration detection—many illicit laboratories have tweaked fentanyl’s molecular structure, selling fentanyl variants under names like “China white” and acetyl fentanyl, the latter of which was responsible for a cluster of deaths recently in Rhode Island and Pennsylvania.

With so many variants on the market, users have no way of knowing the strength of the drugs they are using, which raises the risk of fatal overdose.

Schnur said Patrick tried several medications and rehabilitation programs as he tried to quit—and apparently stayed off heroin for several years before his overdose.

Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI), has studied heroin and fentanyl addiction for many years. He said while there are treatments such as naloxone for opioid overdose or methadone for addiction, many people still relapse.

“These treatments are working for some people, but there is clearly a gap that needs attention,” Janda said.

Janda and his colleagues at TSRI have been working on an innovative strategy to curb addiction and even prevent fatal overdoses: vaccines.

In 2013, the researchers reported successful preclinical tests of a vaccine to neutralize heroin. Now, in their latest study, published recently in the journal Angewandte Chemie, they show how a new vaccine might stop fentanyl and similar opioids from reaching the brain.

“We want to stay one step ahead of these clandestine laboratories making illegal opioids for black market demand,” said Janda. “The importance of this new vaccine is that it can block the toxic effects of fentanyl, a first in the field.”

Blocking the High

Heroin and fentanyl provide a “high” by activating the opioid receptors in the nervous system, where they trigger feelings of euphoria and reward. Opioids can also be too relaxing. The cause of death in heroin and fentanyl overdose is the suppression of the autonomic breathing system in the brain—people stop breathing, go into respiratory arrest and die.

Janda’s vaccines are based on the hypothesis that if you can get the body’s own immune system to recognize and neutralize drug molecules, you could keep them from ever reaching the brain. This would prevent users from experiencing a “high” and, in theory, discourage drug-seeking and drug-taking behavior.

The Janda laboratory’s new anti-fentanyl vaccine cocktail contains a molecule that mimics fentanyl’s core structure. When exposed to the vaccine, the immune system is “trained” to produce antibodies to neutralize fentanyl and its effects.

In the new study, the vaccine was tested in mouse models of fentanyl addiction and overdose. Mice were given three vaccinations, each two weeks apart—like a series of booster shots. By studying antibodies in the blood, the researchers saw that the immune system was successfully neutralizing fentanyl for months after the last injection. In further tests, the researchers observed that vaccinated mice given fentanyl did not demonstrate “high” behavior (such as ignoring discomfort).

In fact, a 30-fold greater-than-normal dose of fentanyl was necessary for the drug to activate neural circuits in vaccinated mice. Remarkably, antibodies generated by the vaccine protected against overdose, neutralizing lethal levels of fentanyl.

“To the best of our knowledge, our active vaccine is the first to ablate lethal doses of any drug of abuse,” said TSRI Research Associate Atsushi Kimishima, co-first author of the new study with TSRI graduate student Paul Bremer.

“This surprised us the most,” added Bremer.

Importantly, the potential vaccine protects against virtually all fentanyl derivatives and does not cross-react with other drug classes, such as oxycodone. This means those vaccinated would still have painkiller options in medical situations.

The researchers said the next step in this research is to design an even more potent vaccine, perhaps a combined anti-fentanyl and heroin vaccine. “Since heroin is often cut with fentanyl derivatives, a combination vaccine targeting both opioids would be worth investigating,” said Bremer.

Janda hopes these vaccines may one day go into human clinical trials, along with similar vaccines his laboratory has developed against cocaine and nicotine addiction.

Helping Loved Ones

Patrick Schnur loved computers, and he loved math, gaming and skiing. In high school, Patrick decided he wanted to be a pharmacist. Both his parents had studied biology and worked in the pharmaceutical field, and the apple didn’t fall far from the tree, his mom said.

Starting in high school, Patrick also developed anxiety and depression. He would have panic attacks if he were called on in class—sweaty palms, heart racing and a choking feeling. He shared these issues with his parents, as he would many times when seeking help in the years to come.

A psychiatrist prescribed Patrick anti-anxiety medication, and it helped. Instead of feeling anxiety, Patrick was suddenly outgoing. He also made new friends and started going out to night clubs. In 2010, when hanging out with an older sibling’s friends, Patrick tried injecting heroin for the first time.

“Patrick said that it was like being in a warm cocoon,” Schnur said, “and when he looked in the mirror he smiled. That is how it all started.”

Schnur doesn’t know why Patrick used heroin again after years of staying clean and dedicating himself to school and exercise. But, like Janda, Schnur knows her son’s addiction was a brain disease out of his control. Patrick couldn’t just get “over it,” she said.

Schnur had read about Janda’s heroin vaccine research and hoped it might one day help her son. She knew he would try anything to stop his addiction.

Once, when facing an intense craving, Patrick decided to commit suicide. He drove his car more than 100 miles an hour toward an embankment, missed and crashed into a concrete median.

Amazingly, he was pulled from the car with only minor injuries. "I want to live!” Patrick said at the hospital. "I really want to live!"

Authors of the Janda’s new study, “Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs,” included Joel E. Schlosburg, Bin Zhou and Karen C. Collins of TSRI. To view the abstract of the paper, see http://onlinelibrary.wiley.com/doi/10.1002/anie.201511654/abstract. To support addiction research at TSRI, go to https://support.scripps.edu





Send comments to: press[at]scripps.edu



schnur-janda
Kathy Schnur, who lost her son to heroin addiction, visits the laboratory of Professor Kim Janda to learn about his work on vaccines against drugs of abuse. (Photo by Cindy Brauer.)