Fiddling With Gene Responsible For "Asian Flush" Could Treat Alcoholism

Alcohol is one of the most commonly abused substances in the world, causing approximately 3.3 million deaths every year. Lijphoto/Shutterstock

Gene therapy has already been used with great success to help treat humans with serious conditions, including everything from cystic fibrosis to cancers. One of the most the fascinating promises is that it could even be used to treat some forms of substance abuse.

New research has now looked into how gene therapy could be used to treat alcoholism, by mimicking a natural mutation commonly found in East Asian people that makes them more intolerant to alcohol, popularly known as the “Asian flush” or “Asian glow”.

As described in a study published in the journal Human Gene Therapy, the gene therapy works by blocking the expression of one of the main enzymes that break down alcohol, resulting in the accumulation of the toxic byproduct acetaldehyde in liver cells. This buildup of acetaldehyde can leave you feeling fairly ill, with symptoms like a red flushed face, blotchy skin, dizziness, and palpitations, leading people to avoid alcohol.

Approximately half of East Asians have the gene variant, mitochondrial ALDH2, which results in a less functional dehydrogenase breakdown. It’s most common among Chinese, Taiwanese, Japanese, and Korean people, and around a third of people with the gene variant experience these moderately unpleasant symptoms. As such, it has been associated with reduced rates of alcoholism among certain East Asian populations.

To mimic this effect, scientists from the University of Chile and University of North Carolina tested out this idea by using a virus to “deliver” a nucleic acid fragment into human liver cells in the lab. This resulted in reduced expression of the ALDH2 enzyme by up to 90 percent.

"Alcohol and other substance use disorders, together with the associated problem of suicide, are driving an alarming increase in mortality among middle-aged Americans in recent years," said editor-in-chief of the journal, Terence R  Flotte of the University of Massachusetts Medical School, in a statement.

"What has not often been recognized is that genetic factors account for over 70 percent of the risk of alcoholism, based on twin studies. This suggests that genetic therapy would be a logical approach. These investigators have targeted one of the best established genetic contributors and demonstrated strong proof-of-concept data with a rAAV vector-mediated shRNA approach. This bodes well for future development of this therapy."

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