Image courtesy of Flickr Creative Commons user nexthttp.
University of Texas researchers are looking at how alcohol affects brain receptors and gene expression in hopes of treating alcohol addiction.
University of Texas researchers are looking at how alcohol affects brain receptors and gene expression in hopes of creating a drug to help treat alcohol addiction, a condition that affects about 18 million Americans to some degree, according to the National Institute of Alcohol Abuse and Alcoholism.
“Alcohol is so widely available, it’s not an illegal drug, and yet we know far less about how it works compared to drugs that are illegal,” said John Mihic, an associate professor in the College of Pharmacy and Natural Sciences as well as a co-investigator. “I’ve always found that kind of ironic.”
The researchers are all associated with UT’s Waggoner Center for Alcohol and Addiction Research, and are looking for ways to reduce alcohol consumption by altering gene expression. Another goal is to how alcohol alters brain receptor function. The research is in its starting stages with alcohol loving lab rats serving as a model for human alcoholics. A $3.3 million five-year grant from National Institute on Alcohol Abuse and Alcohol is funding their research.
A part of Mihic’s portion of the research project focuses on finding peptides, very small proteins that can either act as alcohol-mimics or alcohol blockers at the glycine receptor. Although it’s only one of the many receptors activated by alcohol, research has shown it’s likely to play a large part in a range of alcohol-induced behavior, like uncoordinated behavior, slurred speech and blurred vision. Because alcoholics drink largely because it creates positively reinforcing feelings, Mihic said his thinking is that if the symptoms can be blocked, the craving to drink may not be as strong.
To find promising peptides Mihic and his team scan billions of short peptide sequences using a technique called, “phage array.” The technique gets its name from using proteins found on the protein coat of viruses as building blocks to create the unique peptide sequences. Phage array is a common scanning technique in cancer research but almost unheard of in neuroscience, said Mihic, where many drugs meant to help alcohol abused have come to be based on accidental discovery.
“Relying on serendipity seems to be a really stupid approach,” said Mihic. “I thought, ‘Wouldn’t it make more sense to take a rational approach?’”
If a peptide does well at blocking the receptor in a petri dish it’s tested next in rats. Human trials, however, are something much farther down the road—if the peptide can make it that far.
“It’s one of these things that could fail at any point of the developmental path so if it didn’t work in monkeys we would have to basically start over again,” said Mihic, “which is why it costs a billion dollars [to develop an FDA approved drug].”
Another prong of the research project focuses on what genes are expressed by alcohol and how their expression can be altered.
Igor Ponomarev, a research assistant professor in the College of Pharmacy and Natural Sciences as well as a co-investigator, is studying what genes are activated in the brain when exposed to alcohol and drugs that alter how rewarding drinking feels by affecting gene expression.
“If alcohol doesn’t feel as rewarding then the animals won’t drink as much,” said Mihic on the goal of Ponomarev’s work.
The final area of research in the project, led by UT research scientist R. Dayne Mayfield, is looking at how drinking alcohol influences microRNA expression in the brain, and if changing their expression patterns can make the rats drink less alcohol. MicroRNAs can either increase gene expression or act like roadblocks depending on the distinct situation.
There are currently three FDA approved drugs to treat alcoholism on the market today, but there are some serious flaws with all of them. Two of the approved drugs only work well on subsets of patients. The third one, Disulfiram, works more as a threat than a medication, causing the person to become violently ill if they drink alcohol.
“Basically, you’re holding a hammer over somebody’s head and you’re saying ‘if you drink it’s going to hurt’,” said Mihic.
Although the research is just starting, Mihic says he hopes that the research could help lead to the development of a drug that aids in recovery by preventing a person from finding alcohol rewarding resulting in less of an urge to drink it.
Ilana Zivkovich, the director of clinical development at local rehabilitation center Austin Recovery, says that she’s interested in what the research will lead to, but is skeptical about possible outcomes.
“It’s very difficult to develop a drug to treat drug problems without developing some secondary addictive tendencies,” said Zivkovich.
Although some patients at Austin Recovery are prescribed medicine to help them with their rehabilitation, a large focus of center is helping individuals take control of their own lives and emotions through therapeutic means like counseling, art and music. Approximately 70 percent of Austin Recovery’s patients enter the center with some form of alcohol dependency, according to Zivkovich.
Mihic said that if a drug is eventually developed it will likely be a useful tool in the recovery process, not an instant cure-all.
“My gut feeling is that there is no popping a pill when getting rid of alcoholism,” said Mihic. “I can’t believe that it would be that simple.”