Mutant Worms That Don’t Get Drunk Provide Promise for Alcohol Treatment

Oh they showed all the signs of alcohol intoxication — the weaving, the poky movement. That was before the worms had brain surgery.

By tweaking a molecular channel in the tiny animal’s brain, neurologists have found a way to genetically alter a worm so it doesn’t get drunk after consuming alcohol, a potentially promising finding in the treatment of addiction.

After ingesting alcohol, the worms in the experiment would move more slowly, if at all, and suffer reproductive disruption. But researchers at the University of Texas at Austin reported that they were able to modify the worms’ genetic makeup in a way that prevented alcohol from binding in the brain, preventing intoxication.

Their new study, published July 16 in The Journal of Neuroscience, is not for the casual reader. But one of the research authors, Jon Pierce-Shimomura, assistant professor at the University of Texas’ College of Natural Sciences and Waggoner Center for Alcohol and Addiction Research, said the upshot is a hopeful one.

“Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target [in the brain] to prevent problems in alcohol abuse disorders,” Pierce-Shimomura said. “However, it remains to be seen which aspects of these disorders would benefit.”

An “alcohol target” is one of several impulse-transmitting cells of the nervous system that binds alcohol in the brain.

And the altering of such a human neuronal molecule in an animal — spawning mutant worms — is a first, researchers report. Such a drug could potentially be used to treat alcoholics because it would counteract the intoxicating and potentially addicting effects of the alcohol.

Pierce-Shimomura also envisions a more fanciful application of the research, that of a “James Bond drug” that would enable a spy to drink his opponent under the table and walk away unfazed.

Help for Alcoholics

Earlier this year, the World Health Organization issued an alarming global report that showed one person dies of an alcohol-connected illness every second. In the U.S., national statistics reveal that as many as 18 million people have issues with alcohol abuse and that about 88,000 people die every year due to excessive drinking.

Authors of the WHO study published in the Journal of the American Medical Association found that despite those daunting figures, prescription drugs that curb alcohol cravings are “considerably underused.”

Once exposed to alcohol, the brain craves it, which is a primary cause of addiction and of relapse from sobriety. Unlike drugs such as cocaine that target one part of the brain, alcohol has multiple and complex impacts on the brain. Studies have shown that the medications naltrexone and acamprosate, which have been around for years, may decrease those cravings and, when combined with counseling, reduce drinkers’ return to alcohol.

So researchers are coming at the processing of alcohol to ultimately ease the body’s reaction to withdrawal from it in hopes of improving the rate of addiction recovery.

Enter the Caenorhabditis elegans.

Grad student and lead study author Scott Davis discovered that a specimen of this particular type of worm did not get drunk on alcohol, and that it had a mutation; so the neurologists set out to see if altering a similar but human gene and inserting it into the worm would also prevent signs of intoxication. And it repeatedly did.

“This is the first example of altering a human alcohol target to prevent intoxication in an animal,”  Pierce-Shimomura told Science Daily.

What’s more, the researchers “got lucky” in tampering with the particular neuronal channel, which regulates other functions, because those other functions were not impacted, the researchers told Science Daily. Only its response to alcohol was changed.

Worm Brain Surgery Broken Down

Imagine the size of a worm’s brain and you get a sense of how micro this research was, and how abstract the abstract was summarizing the findings. The scientists tweaked the molecular channel in the brain — common to most organisms including humans and worms — that cues intoxication symptoms.

Steven E. Franklin, spokesman for the university’s College of Natural Sciences, took a crack at simplifying the research findings for the non-scientist — or how he might explain it to his mother:

“The researchers were studying a worm used in many scientific studies. Normally these worms show signs of intoxication when exposed to alcohol (basically, they have trouble moving and laying eggs). They found that worms with a small mutation in a particular gene, which is similar to one found in humans, would no longer get intoxicated when exposed to alcohol. They then took the human version of the gene (which is slightly different), changed it in the same way that the worm gene had been altered, and stuck this into the worms.

“The worms still would not get drunk.

“They think that the mutation in the gene is preventing the alcohol from attaching in the brain and causing drunkenness. Also, the mutation did not cause any other side effects. If they take the mutated version of the human gene and put it into mice, they can see if the change also affects other problems that alcoholics might have, like cravings or withdrawal symptoms.”

As informative as the worm genes proved, Davis told Science Daily they didn’t reveal how other alcohol withdrawal symptoms might be affected.

The research team is still not sure about certain parts of the gene alteration, Franklin said, and to understand how it might apply to humans, they will next be joined by other researchers in testing it with mice. In doing so, the academics hope to better understand how other symptoms of alcohol withdrawal might be reduced or eliminated with either the same or a different genetic alteration.

There is still hope.

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