“We didn’t see any signs that their alcohol consumption would return to baseline levels, so we think this epigenetic editing may have lasting effects,” Pandey said. “I think more work needs to be done on how to translate this into humans for therapy, but I have high hopes.”
for testing arc Genes are indeed responsible, and the researchers also designed a Crispr injection designed to reduce its expression. They tested it on mice that had not been exposed to alcohol during adolescence. After the injection, the mice were more anxious and drank more alcohol than before.
This research raises the possibility that our molecular memory can be modified or even erased. “I’m impressed that this work demonstrates the feasibility of altering a gene’s memory of its experiences,” said Fyodor Urnov, UC Berkeley professor of genetics and scientific director of the UC Berkeley and UC San Francisco Institute for Innovative Genomics. .” But, he continued, rats are not humans, and we shouldn’t jump to conclusions. “The distance between curing mice with epigenetic editors and injecting alcohol addiction is enormous,” Urnov said. “I think we’re a long way from being eligible for rapid injections into their amygdala in people with mild drinking problems.”
That said, Urnov, who is also co-founder of the epigenetic editing company Tune Therapeutics, could see experimental therapies like this being tested in alcohol-addicted patients who have relapsed from treatment multiple times and have no other treatments choose.
However, as with editing genes directly, tweaking their expression can have unintended consequences.because arc is a regulatory gene involved in brain plasticity, and altering its expression may have effects beyond alcohol addiction. “We don’t know what other behaviors this change alters,” said Betsy Ferguson, a professor of genetics at Oregon Health and Science University who studies epigenetic mechanisms in addiction and other psychiatric disorders. “It’s a balance between finding something that works and something that doesn’t disrupt everyday life.”
Another complicating factor is that drinking alcohol can alter the expression of dozens or even hundreds of genes over time.In people’s eyes, it may not be as simple as turning up the expression arc, which is just one of them.Although it looks like the solution might be to adjust all Among these genes, manipulating the expression of many genes simultaneously can cause problems. “Knowing that behavior, including alcohol use, is regulated by many genes, is really a difficult problem to solve,” Ferguson said.
It is unclear how long the effects of this editing will last. Naturally occurring epigenetic changes can be temporary or permanent, Ferguson said. Some can even be passed on to future generations. Overall, she finds the idea of using epigenetic editing to treat alcohol addiction fascinating, but she hopes to see the results replicated and the Crispr treatment tried in larger animals that more closely mimic humans.
That day may not be too far away, as several companies have recently launched the commercialization of epigenetic editing.At Navega Therapeutics in San Diego, researchers are studying how to reduce the SCN9A. When it is highly expressed, it sends out a lot of pain signals. But simply deleting this gene is a bad idea, because a certain level of pain is useful; it signals when something is wrong with the body. (In rare cases, with SCN9A Mutations that effectively inactivate them are immune to pain, which leaves them vulnerable to imperceptible damage. ) In Navega’s experiments, epigenetic editing in mice seemed to suppressed pain for months.
Meanwhile, Urnov’s Tune Therapeutics plans to use epigenetic editing for a wide range of diseases, including cancer and genetic disorders. While Urnov doesn’t see epigenetic editing as an antidote to alcoholism, he thinks this proof-of-concept study shows that it’s possible to rewire our genetic experience to reverse some of the damage caused by early alcoholism. “Frankly, given that we now have genome editing to counter the deleterious effects of drugs, right where the drug imprints its memory on the brain, that’s a power,” he said.
