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On August 15, a team of scientists from the Florida-based Scripps Research Institute and the University of Kansas published an article in Science, a peer-reviewed academic journal, in which they announced a potentially groundbreaking genetic discovery. The researchers believe that they may have found a way to diminish the addictiveness of prescription opioids. If so, a genetic solution to opioid addiction may exist.
The research study began when the scientists mutated over 900 genes in a group of worms called nematodes. The purpose of the mutations was to identify genes which affect sensitivity to opioids. In order to test opioid sensitivity, the scientists first modified the nematodes’ DNA to express mu-opioid receptors (MOR). These receptors exist naturally in humans and other mammals and allow opioid-based medications to affect the nervous system. The modification caused the worms to react to morphine, a common opioid painkiller.
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The scientists eventually discovered that the nematodes responded less noticeably to morphine as a result of a mutation in FRPR-13, a gene which corresponds to a gene in mammals that is responsible for the production of the protein GPR139. The scientists then learned that GPR139 inhibits MOR activity, so the scientists started to experiment with it in mice. When the researchers modified DNA in mice to activate the production of GPR139, they found that the mice stopped taking morphine. Since GPR139 reduced or eliminated the effects of morphine on the mice, they lost interest in it. In other words, the genetic modification prevented the mice from continuing to take opioids and becoming addicted.
The scientists then coded the DNA in other mice to prevent the production of GPR139, and the results were even more remarkable. For mice that lacked GPR139, the effectiveness of morphine as a painkiller increased. However, the mice also exhibited minimal withdrawal symptoms even after prolonged exposure.
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This scientific study may expand scientists’ understanding of how genetics affect opioid addiction and withdrawal. According to Professor Kirill Martemyanov, one of the authors of the Science article, “a study like this makes it clear that even though we may think we know everything there is to know about the opioid response, we’re actually just scratching the surface.”
Although opioids are the most effective medications for treating pain, they are also capable of causing severe addiction disorders which sometimes culminate in fatal overdoses. Additionally, the symptoms of opioid withdrawal often cause patients to become dependent on opioids. For these reason, scientists have been trying to develop alternative painkillers, but if GPR139 makes it possible to develop opioids which are effective yet do not cause withdrawal, the problem of opioid dependence may be solved. In the words of the study itself, “GPR139 could be a useful target for increasing opioid safety.”
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