OSU-CHS professor says CRISPR is key to stopping opioid overdose deaths

Thursday, June 18, 2020

In the U.S., a person dies of an opioid overdose every 13 minutes­— that’s more than 100 people a day who lose their lives to this epidemic. But a researcher at OSU Center for Health Sciences thinks there is way to stop the overdose deaths using the newest technology in genetic science, CRISPR.

Dr. Craig W. Stevens, professor of pharmacology at OSU-CHS, authored a recent scholarly paper in the Journal of Neuroscience Research that proposes altering opioid receptors in respiratory neurons utilizing CRISPR technology in order to prevent opioid overdose deaths.

“There are opioid receptors in all kinds of places in the brain including respiratory neurons. So when opioids hit those particular receptors on those particular neurons that control respiration they inhibit those neurons from firing,” Stevens said. “It’s the main effect that causes death because those respiratory neurons are what keep you breathing.”

Respiratory depression is when the lungs fail to exchange carbon dioxide, what we breath out, for oxygen, what we breath in, resulting in short shallow breathing.

“Once opioids decrease the breathing, then the organ systems become hypoxic, you can go into respiratory arrest, the brain doesn’t work to drive respiration, and the heart eventually stops beating. The real key and the real reason of opioid deaths start with respiratory depression,” he said.

Stevens earned his Ph.D. in Pharmacology from the Mayo Graduate School of Medicine studying opioid tolerance. Shortly after, he came to the Department of Pharmacology and Physiology at OSU-CHS where he has served as an assistant professor, professor and department chair.

“I’ve been in the opioid field for about 35 years. As an opioid pharmacologist, it’s always been my area of interest and expertise,” he said.

When the opioid epidemic ramped up across the state and across the country, Stevens joined the Coalition Against Prescription and Substance Abuse of Tulsa (CAPSAT) and served as the organization’s chair for several years.

“That made me more aware of the clinical situation,” he said. “The number of opioid overdose deaths has doubled since 2010 and it’s expected to double again in the next 10 years. In 2017 alone there were 47,000 deaths by opioid overdose. That’s just in one year.”

Medical professionals have tried using NARCAN in emergency situations and Prescription Drug Monitoring Programs, but Stevens said it’s not enough. 

“These approaches we’ve tried so far, while they’re helpful and I’m sure saved lives, they haven’t made a significant impact. Nothing we’ve instigated has really made a dent in the numbers,” he said.

Stevens wanted to bring his 30-plus years of knowledge of pharmacology and opioid receptors to help solve the problem of overdose deaths by using the most modern tools in the industry.

Gene therapy has been around for almost 20 years, Stevens said, but the problem with older gene therapy methods are they couldn’t be put in the exact genome where it was needed, it was more like a shotgun approach. The CRISPR microinjection would target just the opioid receptors in the respiratory neurons.

“You don’t have to worry about off-target effects like turning on cancer genes or turning on various disorders because you’re not just changing the genome willy-nilly where you could knock out an important gene or alter the expression of another gene,” he said. “But by being targeted, you can just hit the opioid receptor gene in the respiratory neuron and therefore turn off that gene so it won’t make opioid receptors. You can’t die because it can’t inhibit the respiratory neurons by using opioids, there’s no receptor to find the drug.”

Stevens said CRISPR’s super-targeted gene alteration would mean no change to opioid receptors on other neurons like pain neurons. Patients would still receive the benefit of opioids without the risk of overdose, so it could be used in conjunction with substance use disorder treatments.

“It dovetails quite nicely with medication-assisted treatment because that’s going to help decrease the opioid use, it’s going to help chronic pain patients prevent their addiction. But at the same time, this is a safeguard that prevents death,” he said, so someone who is taking buprenorphine as part of a medication-assisted treatment (MAT) for opioid addiction but relapses won’t die from an overdose. “They’ll be alive and they can go back to treatment. This would almost be a backup program to medication-assisted treatment to try to get people to lower their dependence on opioids.”

Since the paper was published in May, Stevens said he’s already had interest from other researchers and scientists to collaborate on the next phase of the research, preclinical trials, where a CRISPR construct is developed to target opioid receptors in respiratory neurons of rats or mice.

Then after about five to six years of preclinical trials, approval would be sought for phase one of clinical trials.

“I think of this as this generation’s moonshot. In a decade you could have a viable clinical method to stop the opioid epidemic,” he said, but he won’t be able to do it alone. “It will take a large group of dedicated scientists and institutions to actually pull this off. Like the moonshot, it took numerous agencies and industries to get us to the moon by 1969. This is kind of the same thing, a national effort brought together, and we could end the opioid epidemic once and for all.”

MEDIA CONTACT: Sara Plummer | Communications Coordinator | 918-561-1282 | sara.plummer@okstate.edu