Thursday, Oct. 10, 2019
When battling opioid use disorder, some medications can give patients unwanted side effects, while others can have addictive properties of their own. Virginia Commonwealth University researchers are studying new alternative medications that could give patients hope.
VCU’s School of Pharmacy, School of Medicine and C. Kenneth and Dianne Wright Center for Clinical and Translational Research are studying treatment options for intervening in opioid overdose cases or helping those struggling with opioid addiction to stave off cravings and avoid relapse.
The three projects were awarded $2.6 million last month through the National Institutes of Health Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, to improve treatment for opioid addiction. Since 2014, VCU has consistently been in the top 10 organizations in funding from the National Institute on Drug Abuse, which played a major role in founding the NIH HEAL Initiative.
“[This funding is] in line with the outstanding research that’s taking place across VCU in the area of addictions,” said F. Gerard Moeller, M.D., director of the Wright Center and division chair for addiction psychiatry.
VCU’s awards are part of 375 grant awards across 41 states made by the National Institutes of Health in fiscal year 2019 to apply scientific solutions to reverse the national opioid crisis.
More than 130 people died every day from drug overdoses in the U.S. in 2017, according to the Centers for Disease Control and Prevention. The NIH launched the HEAL Initiative in April 2018 to improve prevention and treatment strategies for opioid misuse and addiction and enhance pain management.
“It’s clear that a multipronged scientific approach is needed to reduce the risks of opioids, accelerate development of effective non-opioid therapies for pain and provide more flexible and effective options for treating addiction to opioids,” said Francis S. Collins, M.D., Ph.D., director of the NIH who launched the initiative. “This unprecedented investment in the NIH HEAL Initiative demonstrates the commitment to reversing this devastating crisis.”
Finding medication alternatives
Four VCU researchers are leading a study that received $1.6 million for its first two years to reformulate levomethadyl acetate, an FDA-approved opiate dependence medication, into a formulation that could be patented for pharmaceutical companies to distribute.
Unlike methadone, an opiate medication that requires daily doses, levomethadyl acetate, which is also known as LAAM, can be used a few times a week for treatment. Distribution of levomethadyl acetate was discontinued in 2003 because of declining sales after buprenorphine’s introduction as a prescription treatment and concerns about cardiac effects. Studies published in 2003 and 2007 in the peer-reviewed journal Addiction showed LAAM to be more effective than methadone in suppressing heroin use.
“We aim to develop novel formulations of LAAM as proprietary products to provide additional effective medications to the few existing products available to treat opioid use disorder,” said primary investigator Qingguo Xu, Ph.D., assistant professor of pharmaceutics in the School of Pharmacy.
Researchers are seeking to give pharmaceutical companies a reason to bring back the medication as an additional option that could work better for some patients than methadone or buprenorphine.
“From the patient perspective, it’s a desperately needed drug,” said Charles O’Keeffe, professor of pharmacology and toxicology in the School of Medicine and a primary investigator. “But from an economic perspective, no company would have an incentive to expend the necessary development funds unless there was some market exclusivity period to allow them to recoup those costs.”
VCU researchers, including fellow primary investigators Moeller and Matthew Halquist, Ph.D., assistant professor of pharmaceutics and director of the Bioanalytical Laboratory in the School of Pharmacy, hope to generate a medication and offer a patent through this project that will encourage pharmaceutical companies to pick up the drug as an additional treatment option.
“It gives you that opportunity to contribute to this major issue going on in the country,” Halquist said of the study. “VCU is at the forefront of dealing with opioid addiction. It’s a great opportunity for the School of Pharmacy and the School of Medicine to work together; we have a great, dynamic team.”
Quamrun Masuda, Ph.D., assistant director of the VCU Center for Compounding Practice and Research and associate professor of pharmaceutics, and Albert Arias, M.D., associate professor of addiction psychiatry in the School of Medicine, round out the VCU research team for the project, along with collaborator Xiuling Lu, Ph.D., associate professor of pharmaceutics at the University of Connecticut.
Developing a new drug
Yan Zhang, Ph.D., professor of medicinal chemistry in the VCU School of Pharmacy, is overseeing a study that received $1 million for its first year of preclinical research to develop an overdose medication with fewer side effects and fewer addictive properties than leading overdose medications.
“Our goal is to develop new therapeutics to treat opioid abuse and addiction,” Zhang said.
Initial studies of mu-opioid receptor modulators, which are one of three opioid receptors that trigger the brain’s rewards system and are thought to contribute to addictive behaviors, have been promising, showing fewer withdrawal symptoms than in other medications, Zhang said. His team has identified several mu-opioid receptor modulators as leads for the development of this new medication.
A third treatment to help reduce cravings is being developed in preclinical trials by researchers at the University of Texas Medical Branch at Galveston. Moeller, who will conduct the clinical trials for this third study, said he thinks this could be a good pairing with other medications to prevent relapse.
Moeller said there has been data so far to suggest compounds that affect the ghrelin receptor system in the body can reduce alcohol cravings. His counterparts in Galveston, led by Kathryn Cunningham, Ph.D., UTMB’s vice chair of pharmacology and toxicology and director of the Center for Addiction Research, will test if this non-opioid medication might stop opioid cravings.
Following outcomes of the two-year preclinical studies, Moeller could lead clinical trials for these medications at the VCU Center for Compounding Practice and Research starting as early as 2020.
Moeller will oversee the clinical trials for all three projects if they meet preclinical milestones. VCU School of Pharmacy and School of Medicine researchers will lead the preclinical portions of two projects.
“In 2018, our No. 1 source of NIH funding for all of VCU was the National Institute on Drug Abuse showing that we really are leaders in the addiction research realm across the country,” Moeller said.
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