“Asian Flush” Gene Could Help Battle Alcoholism – Study Says
Everyone is obviously different once they have had a drink or two. But it’s a whole different ball game when someone has been drunk for two days straight and it’s the middle of the week. Alcohol can turn someone into someone they aren’t. More so than the average person who gets a little drunk off a glass of wine.
Being an alcoholic or alcoholism for that matter, is not something that should be joked about. There’s no such thing as one drink. It is an addiction that can take over one’s body; alcohol is a drug that can be just as addictive as any other drug. Alcohol is the most commonly used addictive substance globally and causes some 3.3 million deaths every year, which approximates to 5.9% of all deaths.
There are currently three approved medications in the U.S. for treating alcohol dependence—disulfiram, naltrexone, and acamprosate. However, none is widely prescribed because they have limited efficacy, cause side effects, and patient compliance is poor.
Now, a new study has, in an attempt to aid alcoholics, has looked into how gene therapy could feasibly help to treat alcoholism by causing unpleasant
physical side effects in individuals who imbibe.Ethanol is metabolized in the liver in two stages: first the oxidation of ethanol to form acetaldehyde. This reaction is catalyzed by the cytosolic enzyme alcohol dehydrogenase (ADH). The acetaldehyde is then converted to acetate by a mitochondrial isoform of the enzyme aldehyde dehydrogenase, ALDH2.
Approximately 50% of the Asian population are heterozygous and have a normal copy of the ALDH2 gene and a mutant copy that encodes for an inactive mitochondrial isoenzyme (ALDH2*2). These individuals have a diminished capacity to metabolize acetaldehyde. Therefore, acetaldehyde accumulates in the blood after ethanol consumption, producing effects including facial flushing, dizziness, hypotension, and palpitations- commonly known as the “Asian flush” or the “Asian glow”. This promotes a reduction in alcohol consumption and protection against alcoholism.
ALDH2 is a recognized target for treating alcohol dependency. Therefore, the researchers developed an short hairpin (sh) RNA designed to silence the expression of ALDH2 and can be delivered to cells using a self-complementary AAV2 (scAAV2) vector. They then tested the shRNA in both a specially developed ALDH2-expressing human liver cell line, HEK-293/ALDH2, and to HepG2 liver cancer cells.
This resulted in vector-delivered shRNA significantly reducing ALDH2 transcript and protein levels.
“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,” says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. “What has not often been recognized is that genetic factors account for over 70% 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.”
