ming xu

Ming Xu, professor of critical care and anesthesia at the University of Chicago. 

Stem cell researchers at the University of Chicago believe we could be close to a future without drug addiction after recent progress on a revolutionary new treatment.

It has been well-documented that drugs can affect one’s brain, releasing the pleasure chemical dopamine and causing a dependence on the drug to develop. But using a novel molecular therapy treatment, U. of C. neurobiology professor Ming Xu believes it is possible to manipulate the substance abuse process. 

“(The treatment) didn’t come from me initially,” said Xu. The process is based on an already-existing technique in which the DNA that produces therapeutic molecules — namely Butyrylcholinesterase, which degrades cocaine in the body, and glucagon-like peptide 1, which reduces the motivation to take cocaine — is isolated and then delivered into a patient’s skin cells. This is done by using a type of molecular scissor: an agent added to the cells that separates the DNA through a chemical reaction.

There are many advantages to using skin cells. For one, skin grafting surgeries are minimally invasive compared to other surgeries. Because skin is visible from the outside, the genetically modified skin can also be removed easily if there are any complications, which is not possible with other gene therapies. Perhaps most importantly, the skin graft will be stable for many years after the initial grafting, thus providing a long-term treatment for drug abuse.

CRISPR, a gene-editing technology used to isolate specific DNA, is a crucial part of the process. “(CRISPR) is going to revolutionize all biological and medical branches of research and will produce huge benefits for society,” said Xu. Last year, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel prize for pioneering the technique.

Xu faced a problem, however, after he and his team developed the treatment over the past few years: circumventing the rejection of these new skin cells by a patient’s immune system. But a key finding at the U. of C. seems to be the last piece to the puzzle. Xiaoyang Wu, an associate professor in the Ben May Department for Cancer Research at the University of Chicago and a collaborator of Dr. Xu’s, found a way to transplant genetically modified skin cells to normal and immune-competent recipients.

This has meant Xu’s team have been able to experiment with this technique on mice. According to Xu, his next goal is to show it can be effective in humans as well. “In mice it’s wildly successful,” said Xu. “(After the skin graft), you can never induce cocaine abuse…because the therapeutic genes prevent it from happening…and they don’t relapse. 

“(If you) give them lethal doses of cocaine, normal mice will be killed within 5 minutes, (while) grafted mice behave totally normally.”

Xu also described his motivation for seeking to treat addiction. “Drug abuse, in general, is one of the foremost public health problems. It costs society billions and billions of dollars. Economically, (drug addiction) destroys people's lives…Unfortunately, there are very few FDA-approved treatments.” 

Addiction doesn’t only include drugs, either, and it’s very likely that this new treatment will apply to forms of addiction like shopping and gambling. 

“Compulsive drug users… lose control over what they can do, and compulsive (shoppers and gamblers) share very large quantities of these similarities, if they are not identical.”

Both Xu and his colleagues believe this technique is a life-changing medical advancement that could vastly diminish the drug problem in both the United States and the rest of the world. “My goal is to find a useful treatment and show that it has efficacy in humans so a corner of the world can benefit. Then I’m set to retire,” joked Xu.

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