TTUHSC Researchers Developing Lupus Treatment

• By Mark Hendricks
• January 15, 2025
• Research

According to the Lupus Foundation of America, approximately 1.5 million Americans are living with a chronic autoimmune disease that causes the immune system to mistakenly attack healthy cells and tissues. Inflammation that results can damage various parts of the body such as the joints, skin, kidneys, heart, lungs and brain. Although adult men, children and young people can develop the illness, 90% of those living with lupus are women considered to be of childbearing age (15 - 44 years).

A paper published in 2016 by New York University researcher Boris Reizis, Ph.D., found lupus patients have a mutation in a specific protein known as Dnase1L3. Based on that paper, Jon McCord, Ph.D., a recent postdoc at the Texas Tech University Health Sciences Center (TTUHSC) School of Medicine, began studying the protein while working in the lab of Bryan Sutton, Ph.D., from TTUHSC’s Department of Cell Physiology and Molecular Biophysics.

McCord’s and Sutton’s research focused on finding a way to protect Dnase1L3, which would benefit lupus patients. Their idea eventually led them and Peter Keyel, Ph.D., from the Texas Tech University (TTU) Department of Biological Sciences to create plans for a company that will target the root cause of lupus by developing a proprietary treatment the team calls PEGylated Dnase1L3. This pitch took the top spot in October at the Red Raider Startup competition hosted by TTU’s Innovation Hub at Research Park. 

“Dr. Sutton and I were attending a conference in Breckenridge, Colorado and we were talking about this idea to protect the protein,” McCord recalled. “We thought it would be so cool if it worked. When we came back, I tested it and it did work. I suggested that we pursue this idea, because if we don’t do it, I really don’t think anybody else will. Sometimes you have to be your own motivation, and if you’re not willing to pursue your idea, nobody else will either.”

McCord said the enzyme known as Dnase1L3 is a form of Dnase protein that breaks down DNA from dying cells. When cells die, they release DNA into the blood where it’s typically broken down — along with other nuclear debris that can be attached to it — and cleared from the body. However, if a mutation develops that impairs the protein’s function, that DNA and nuclear debris is not broken down and it accumulates. When the body starts to see the DNA debris enough times, it creates an immune response against it.

“That’s a problem because once the body creates an immune response against that DNA in the blood, it triggers an immune response that starts killing more cells, and then more DNA is released because there’s DNA in all our cells,” McCord explained. “This DNA release and response snowballs because there’s more and more accumulating nuclear debris that’s triggering the anti-nuclear debris immune response. As this process goes on, it causes severe symptoms for lupus patients.”

McCord said because very little is understood about lupus pathology, knowing that extracellular DNA triggers this immune response across the board is important for researchers.

“We don’t know if it’s always a genetic response that causes lupus,” McCord said. “We don’t know if it’s always an environmental response that triggers lupus for the first time, but it’s cool to be able to say we know that extracellular nuclear debris is related to all of these cases.”

Although Dnase1L3 can prevent DNA from accumulating in the blood, it is rapidly cleared from the body, which reduces its effectiveness. In addition, most people with severe lupus have antibodies against Dnase1L3, which impairs its ability to function. This new technology addresses these issues by protecting the Dnase1L3 administered to lupus patients.

“We’re protecting the protein from the antibodies and we’re increasing its size so that it’s not cleared as rapidly through the kidneys,” McCord said. “We do that through PEGylation.”

At its core, the team wants to become the force behind this new, patent pending therapy. Over the last several years, McCord and Sutton have met many lupus patients who have motivated them to continue developing PEGylated Dnase1L3 as a therapeutic. The team has plans to pursue commercialization of some of this research through a startup company, spurred by recently winning the Red Raider Startup competition at the TTU Innovation Hub.

“It’s very hard to get an idea off the ground, even if it’s a good idea and you’re giving it to somebody else to pursue,” McCord said. “Luckily, we have a really great innovation support system at TTUHSC through the Office of Research and Innovation and through the TTU Innovation Hub.”