CRISPR Modified Skin Grafts to Treat Addiction? “The possibilities are endless,” says CEO

Published on Monday, January 10th, 2022

AddGraft has developed a platform that uses epidermal progenitor cells of the skin to deliver one or more therapeutic agents. (Image: Bicher)

AddGraft Therapeutics has developed a novel platform that promises the effective treatment of substance use disorders with genetically engineered skin grafts – a unique treatment with countless uses.

Developed by University of Chicago researchers Xiaoyang Wu, Associate Professor in the Ben May Department of Cancer Research, and Ming Xu, Professor of Neurobiology, the platform uses genetically engineered skin cells to deliver therapeutics and has the potential to be long-lasting, highly potent , and minimally invasive treatment that only needs to be administered once.

Outside the lab, this work is currently being commercialized through AddGraft Therapeutics, a startup the duo founded in collaboration with CEO Ryan Meyers, a University of Chicago Booth School of Business MBA candidate with a background in health counseling and venture capital. The company was formed after participating in Compass, a deep-tech accelerator operated by the University’s Polsky Center for Entrepreneurship and Innovation.

“With the Polsky Center’s help, we see greater potential in applying the technology to drug or substance use disorders,” said Wu, AddGraft’s chief technology officer. “There is an enormous unmet medical need and currently no effective therapeutic approaches.”

How does the AddGraft approach work?

Skin stem cells from patients are obtained and modified using CRISPR, a gene editing tool that enables researchers to introduce genes that can produce molecules that significantly reduce the motivation to consume or search for alcohol. The skin cells are then reimplanted into the patient through a skin graft, which acts as a so-called “biomotor” and produces these molecules throughout the life of the graft. In preclinical studies, the engineered skin grafts in animal models protected against drug addiction and overdose.

“With this procedure, we can administer the therapeutic agent to the patient efficiently and safely,” said Wu. “We believe the novel approach can serve as a long-term treatment for patients and protect them from the harmful effects of drug use.”

Although there are already some drugs that are already approved and used in conjunction with behavioral counseling and other approaches, substance re-use is very common. “We hope our approach can prove to be more long-term and stable, probably permanent,” said Wu.

The persistence of the graft is noteworthy as drug compliance is a difficult topic, especially in mental health management, noted AddGraft Advisory Board member and former President and CEO of the Gateway Foundation, Michael Darcy. “This is actually turning the brain off on desire, which is the engine that motivates people who use drugs and alcohol,” he added.

In addition, the platform addresses “all key aspects of alcohol abuse,” said Xu, who acts as AddGraft’s chief scientific officer. These include the development of abuse, relapse, and overdose. “All of this can be prevented by this single genetically modified skin graft,” he said.

While the goal is currently to focus on alcohol abuse, Xu said the platform could also be used to prevent co-use of drugs. Xu said, “My vision, my dream would be to use this novel genetic platform to treat all drug use and co-use, which will greatly improve and promote the quality of life of a large part of society.”

From the laboratory to the market

Although the work is still in the very early stages, the excitement between the team and the youngest investors is palpable. “Many fail for one reason or another, but I think we have some really good factors to work for us,” said Xu. “We have a good team and a very new, unique platform. Above all, there is an enormous unmet need in this area. Our product would really fill a void. I firmly believe in it. “

Xu, who has focused on research into substance use for the past 25 years, found that very little of the findings from his laboratory – and many laboratories in the field – have been commercialized for the benefit of patients. “The public has not benefited from our work,” he said.

Until recently, there was very little innovation in addiction treatment: “It’s been pretty much the same model over the past 40 years,” said Thomas Britton, President and CEO of the Gateway Foundation.

“There are a lot of technologies trying to get into the market today and AddGraft is one of them,” added Britton. “If what they do works and finds widespread adoption, it offers a tremendous opportunity to transform the recovery experience for those who have drug and alcohol use.”

The Gateway Foundation is focused on advancing the science of addiction treatment. For Britton, who is himself in long-term recovery, the work is personal. “I’ve invested a lot of time, energy, and money understanding what leads to better results,” he said. “Early science holds great promise to me.”

One of the biggest obstacles to success, however, is whether the health insurance companies help finance the treatment. “In order for them to make the investment upfront for something that will benefit the payer over the long term, there needs to be a clear value proposition,” said Britton. “If AddGraft can prove the argument with alcohol, the immediate cost of which is dramatic, then I think they can extend the argument to other drugs.

“You have to prove the product works, make people believe it works, and find people who are willing to use it and pay for it. It’s a huge relief, ”he added. “But I think it’s possible.”

The seeds of success

The company recently completed an oversubscribed pre-seed funding round and is working with a regulatory agency consultancy to arrange meetings with the U.S. Food and Drug Administration (FDA) to prepare the technology for clinical trials over the next several years introduce on people years.

Investors in the round included the Chicago Booth Angels Network of Chicago, a nonprofit founded and led by alumni of the University of Chicago Booth School of Business, and Limitless Ventures, an independent growth capitalist interested in improving behavioral mental health is. In addition, AddGraft has been named one of Hello Tomorrow’s Global Deep Tech Pioneers 2021.

“We invested in AddGraft because the technology is innovative and has the potential to have a breakthrough social impact in a growing market. We paid attention because of the connection with the University of Chicago and especially the science team. The researchers have a solid scientific background and the technology is revolutionary – it could change the rules of the game, “said Borislava Karageorgieva, MBA ’04, board director and former president of the Chicago Booth Alumni Club of Chicago and chairman of the Chicago Booth Angels board of directors.

“AddGraft has used cutting edge science in a platform technology. Genetic engineering is turning skin cells into factories that produce molecules that treat addiction and reduce food cravings, ”said Karen Sterling, partner at Limitless Ventures. “If validated in human clinical trials, the effects on everything from alcoholism to nicotine and cocaine addiction could be enormous, saving thousands of lives in the process.”

In the short term, the goal is to get clarification from the FDA on what data is needed to move the technology towards human clinical trials. “That is our number one goal,” said Meyers. The team has also published evidence of the effectiveness of diabetes and weight loss, and is developing these indications in parallel with alcohol use disorder.

“This technology goes far beyond substance use disorder,” said Meyers. “We have the ability to treat a wide variety of conditions that either didn’t have a functioning delivery mechanism, or we can use our technology to dramatically improve the patient experience and treatment effectiveness.”

Pay attention to expected skepticism – is that too good to be true? – Meyers stated that the platform can be programmed to produce any chemical the body is producing or has stopped producing. “The possibilities are endless,” he said. “We have strong evidence and data from our studies that show this will work. That gives us hope and confidence that we have moved past ‘too good to be true’ and into a world where this is real. “

Article by Melissa Fassbender, Deputy Director of External Relations and Science Communication at the Polsky Center. Melissa is a former journalist and has been the editor of various global publications in the areas of drug development, clinical trials, and design engineering. Reach Melissa by email or on Twitter at @melfass.

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