Pritzker Molecular Engineering researchers, under the direction of Professor Jeffrey Hubbell, have demonstrated that their compound can eliminate the autoimmune response associated with multiple sclerosis.
Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have developed a new vaccine that can completely reverse autoimmune diseases such as multiple sclerosis, type 1 diabetes, and Crohn’s disease in clinical tests. immune system.
A typical vaccine teaches the human immune system to recognize things like: virus or bacteria as the enemy to be attacked. A new “reverse vaccine” does the opposite, erasing the immune system’s memory of her one molecule. This erasure of immune memory is undesirable in infections, but it is not desirable in cases of autoimmunity, where the immune system attacks a person’s healthy tissues, such as in multiple sclerosis, type I diabetes, rheumatoid arthritis, and Crohn’s disease. reaction can be stopped.
Reverse vaccines described in a recently published paper natural biomedical engineeringtakes advantage of the way the liver naturally flags molecules in destroyed cells as ‘do not attack’, preventing an autoimmune response against cells that would die by natural processes. PME researchers combined antigens (molecules attacked by the immune system) with molecules that resemble fragments of senescent cells that the liver recognizes as friends rather than enemies. The research team has shown how vaccines can block autoimmune responses associated with diseases like multiple sclerosis.
“We have shown in the past that this approach can be used to prevent autoimmunity,” said Jeffrey Hubbell, Eugene Bell Professor of Tissue Engineering and lead author of the new paper. “But what’s really interesting about this study is that it shows that we can treat diseases like multiple sclerosis after the inflammation is already underway, which is more useful in real-world situations. ”
Unraveling the immune response
The job of the immune system’s T cells is to recognize and eliminate unwanted cells and molecules as foreign to the body, from viruses and bacteria to cancer. Once T cells mount an initial attack against an antigen, they retain a memory of the invader and eliminate it more quickly in the future.
However, T cells can make mistakes and recognize healthy cells as foreign. For example, in people with Crohn’s disease, the immune system attacks cells in the small intestine. In people with multiple sclerosis, T cells begin attacking myelin, the protective membrane around nerves.
Havel and his colleagues knew that the body has mechanisms to prevent an immune response from occurring in response to any damaged cells. This phenomenon is known as peripheral immune tolerance and takes place in the liver. They recently discovered that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) can mimic this process and send the molecules to the liver, where resistance can develop.
“The idea is that you can attach any molecule to pGal and teach the immune system to tolerate it,” Hubbell explained. “Instead of boosting immunity like vaccines do, reverse vaccines can suppress immunity in a very specific way.”
In the new study, researchers focused on diseases like multiple sclerosis, where the immune system attacks myelin, causing weakness, numbness, vision loss, and eventually movement disorders and paralysis. The research team linked the myelin protein to pGal and tested the effectiveness of the new reverse vaccine. They found that the immune system stopped attacking the myelin, allowing the nerves to function properly again and reversing the symptoms of the disease in the animals.
In a series of other experiments, the scientists showed that the same approach works to minimize other ongoing immune responses.
For clinical trials
Currently, autoimmune diseases are commonly treated with drugs that broadly shut down the immune system.
“While these treatments are highly effective, they also block the immune response needed to fight infection, resulting in many side effects,” Havel says. “If we could treat patients with a reverse vaccine instead, it could be more specific and have fewer side effects.”
Although further research is needed to study Hubbell’s pGal compound in humans, an initial Phase I safety trial in patients with celiac disease, an autoimmune disease associated with the consumption of wheat, barley, and rye, has already been conducted. Phase I safety studies are currently underway. Multiple sclerosis progressing. These trials are being conducted by the pharmaceutical company Anokion SA, which is funding the new research and of which Mr Havel is a co-founder, consultant, director and shareholder. The Alper Family Foundation also funded the research.
“Although there is no clinically approved reverse vaccine yet, we are very excited to move this technology forward,” Hubbell says.
Reference: “Synthetic Glycosylated Antigens for Antigen-Specific Suppression of Established Immune Responses” Andrew C. Tremain, Rachel P. Wallace, Kristen M. Lorentz, Thomas B. Thornley, Jennifer T. Antane, Michal R. Raczy, Joseph W. Reda, Aaron T. Alper, Anna J. Slezak, Elise A. Watkins, Chitavi D. Malou, Erika Budina, Ani Solanki, Mindy Nguyen, David J. Bischoff, Jamie L. Harrington, Ravinarayan Mishra, Gregory P. Conley, Romain Merlin, Nathalie Drudre Bosquet, Anne-Sophie Galouet, Roger Legrand, D. Scott Wilson, Stephane Kontos, Jeffrey A. Havel, September 7, 2023, natural biomedical engineering.
DOI: 10.1038/s41551-023-01086-2