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Urdu“Misuse of opioids and methamphetamines leading to addiction is a huge and growing problem, both in the United States and around the globe,” says Cosford, a principal investigator on the grant and professor at Sanford Burnham Prebys. “Our goal by the end of this project is to have a drug ready for clinical development, ultimately showing efficacy in patients and filling a major gap in the available treatments.”
According to the CDC, the number of drug overdose deaths increased by nearly 30% from 2019 to 2020 and has quintupled since 1999. While nearly 75% of the more than 93,000 drug overdose deaths in 2020 involved an opioid, methamphetamine-related overdose rates have steadily risen, nearly tripling in recent years. According to NIDA, 40% to 60% of people with a substance use disorder will have a relapse, putting them at high risk for overdose.
“While misused substances may have different long-term health outcomes, all have some overlapping effects on specific circuits and brain function,” says co-principal investigator Robert Gould, Ph.D., assistant professor of physiology and pharmacology at Wake Forest University School of Medicine. “This, paired with increasing use of multiple substances (including opioids and methamphetamine) reiterates the importance of developing treatments that are effective for multiple substance use disorders.”
While every substance has different effects on cell signaling, all addictive substances rely on similar neurotransmitters in the brain to produce pleasure. This new project will expand on the team’s work on tobacco use disorder, which currently has a drug in a Phase 1 clinical study.
“This is a novel approach to treat substance use disorders, and this funding will allow us to explore it further,” adds Gonul Velicelebi, Ph.D., co-principal investigator and CEO/co-founder of Camino Pharma, LLC.
With the new grant, the researchers will conduct preclinical studies on two potential drug candidates, SBP-1315 and SBP-9220. These compounds inhibit the transmission of glutamate, a neurotransmitter that plays a central role in many normal and abnormal behaviors associated with drug use and relapse.
“By targeting the glutamate system, we may be able to treat opioid and methamphetamine use disorders without some of the risks that come with current treatments, which themselves can be addicting,” adds Douglas Sheffler, Ph.D., a research assistant professor in Cosford’s lab at Sanford Burnham Prebys.
There are several receptors in our brain that serve as landing sites for glutamate. To date, the researchers have focused on the metabotropic glutamate receptor 2 (mGlu2). The new project will test whether targeting mGlu3 in combination with mGlu2 could make the treatment more effective for a wider range of addictions, including methamphetamines and opioids.
“We’re confident we’re on the right track with this, it’s just a matter of studying the biology and learning how to apply it more broadly,” says Cosford. “What is gratifying about this work is that what we find will guide future directions to solve this health crisis. That’s very exciting to us.”
The title of the grant, issued by the National Institute on Drug Abuse of the National Institutes of Health, is, “Characterization, optimization, and development of dual mGlu2/3 positive allosteric modulators for opioid use disorder” (R01 DA057120)
Nicholas Cosford, Ph.D., is a co-founder of Camino Pharma, LLC.
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About Sanford Burnham Prebys
Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 45 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children’s diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.
About Wake Forest University School of Medicine
Wake Forest University School of Medicine (school.wakehealth.edu) is the academic core of Atrium Health and a recognized leader in experiential medical education and groundbreaking research that includes Wake Forest Innovations, a commercialization enterprise focused on advancing health care through new medical technologies and biomedical discovery.
About Camino Pharma, LLC
Camino Pharma is a San Diego–based start-up focused on discovering and developing safe and effective, first-in-class drugs to treat patients suffering from (1) psychiatric disorders that are poorly addressed by current medications, including substance abuse and major depression, and (2) the most aggressive forms of cancer with currently limited treatment options. We target signaling proteins based on emerging biological concepts and discover novel mechanisms for modulating these targets with small molecule drugs. Our leadership team has proven expertise in the relevant target biology as well as extensive experience in drug discovery and development. Our innovative technology platform allows for exploiting inadequately served targets that require a highly adaptive and specialized approach to drug discovery. We intend to find novel cures using our deep understanding in target biology combined with well-tailored, cutting-edge discovery technologies. Visit Camino Pharma at www.caminopharma.com.
