Drug Treatment for Alcohol Abuse Advances to Human Trials in Cross-Institutional Study with UCLA
Repurposing of a familiar medicine may provide a much-needed pharmaceutical treatment to reduce problem drinking.
Research by a soon-to-graduate PhD student at the USC School of Pharmacy has provided data suggesting that a common anti-parasitic medicine can be used therapeutically to help people overcome alcohol use disorders.
Megan Yardley, who will receive her PhD from the Department of Pharmacology and Pharmaceutical Sciences this summer, conducted the research as part of her advanced research training with the TL1 program offered by the Southern California Clinical and Translational Sciences Institute (SC CTSI).
Yardley’s pre-clinical investigations indicate that the drug ivermectin (IVM) – used safely for decades to treat parasitic infections in both humans and animals – may also be used as an alcohol reduction therapy to help alcohol-dependent patients and individuals that abuse alcohol. The mechanism for this new indication is currently under investigation but her data from mouse models suggests that IVM is able to reduce alcohol intake in both social and binge drinking by affecting several different proteins in the brain that alcohol acts upon.
A reported 18 million people in the U.S. have alcohol use disorders, although the actual total is likely much larger because many problem drinkers don’t seek help or receive diagnoses. According to the World Health Organization, in 2012 about 3.3 million deaths, 5.9% of all global deaths, were attributable to alcohol consumption.
But medical solutions have not been easy to find. The three FDA-approved drugs for alcohol abuse are rarely effective. Therapy and programs such as Alcoholics Anonymous, without a pharmacological adjunct, are often unsuccessful, with about a 70 percent relapse rate in the first year.
"Despite the widespread serious social and medical harm attributed to alcohol, there is a lack of effective therapies for alcohol use disorders," said Yardley.
IVM does not appear to have addictive properties, and may prove to be a safe and effective new option to help people break their dependence on alcohol, possibly in combination with therapy or behavioral intervention. “But there are still many questions we need to answer to better understand how alcohol works in the brain to cause problem drinking and how IVM might affect these processes,” said Yardley.
Daryl Davies, PhD, associate professor in the USC School of Pharmacy, has been studying IVM for the past six years, and served as Yardley’s mentor. The SC CTSI supported two of his studies, as well as Yardley’s research as a TL1 scholar.
"None of this new clinical research would have happened had it not been for the TL1 program's support," Davies said. "We've seen that with some effort and creative financing we can pull together small amounts of money to fund early stages of research and then go after larger funding."
Yardley will continue to study IVM in a post-doctoral appointment at the University of California at Los Angeles (UCLA), where she will work with principal investigator Lara A. Ray, PhD, an addiction researcher at the UCLA Department of Psychology, who has recently started to collaborate with Davies on IVM research.
The ongoing research will be jointly supported through a dual-CTSI partnership between the SC CTSI and the UCLA Clinical and Translational Science Institute that reflects the collaboration between Davies and Ray. An SC CTSI grant to Davies covered preclinical toxicology studies at USC, while a UCLA CTSI grant will fund clinical costs for human research participants at UCLA.
"Neither CTSI organization could fund the full study as proposed, but joining together funds from each, we could make it happen," Davies said. "It's a good model – the point of translational science is that you break down boundaries and work in a team fashion."
Yardley has co-authored several publications on IVM and alcohol use disorders, with Davies and other researchers at USC. She collaborated on the recent study with Michael N. Neely, MD, associate professor in the Department of Pediatrics in the Keck School of Medicine.