Fewer trips to the dentist? NYU College of Dentistry wins 2023 STAT Madness with a gel to treat gum disease

It started with mice molars and a hunch.

The New York University College of Dentistry team that won 2023’s STAT Madness competition developed a gel that could eventually replace painful cleanings for gum disease. The gel blocks receptors for a metabolite called succinate, reducing bone loss and inflammation and also changing the makeup of the bacteria found in the mouth.

“We were happy because we think eventually, we hope this treatment will benefit a lot of people,” said Yuqi Guo, an associate research scientist at NYU and one of two lead authors of the study.

STAT’s month-long, bracket-style celebration of biomedical research garnered 145,244 votes for studies on topics from bacteria-resistant catheters to shapeshifting brain fungus and mucus-clearing robotic capsules that deliver drugs. In the end, the NYU team studying gum disease, with 57% of the vote in the final bracket, won out over a team from the Institute for Systems Biology in Seattle that studied ways to predict who develops long Covid.

The NYU team used mice to model periodontitis, a bacterial infection that causes inflammation of the gums. The researchers slipped suture thread in a loop around the molars of the mice to mimic the irritation caused by food stuck in people’s teeth. To mimic long-term disease, some mice had their gums swabbed with bacteria every few days for four weeks to induce periodontitis.

Based on previous studies, Guo, Fangxi Xu, an NYU bioinformatics analyst, and their colleagues hypothesized that a molecule called succinate, produced in a metabolic cycle called the Krebs cycle, might be feeding some of the bacteria that contribute to periodontitis. By studying mice with and without succinate receptors and injecting the mice with succinate, they determined that succinate contributed to bone loss in the mice that developed periodontitis. They then created a gel containing a succinate receptor antagonist that decreased the symptoms of periodontitis.

The study was published in the journal Cell Reports in September 2022. The authors are currently getting approvals for further tests before moving to human trials.

Over 47% of U.S. adults over the age of 30 have some form of periodontal disease, according to the Centers for Disease Control. In early-stage gum disease, known as gingivitis, gums can become swollen and red and may bleed. If not corrected with daily flossing and brushing to clear away the bacteria in plaque — and regular cleanings to remove tartar — gingivitis can progress to periodontitis, in which gums can recede from the teeth and bone may be lost, resulting in teeth falling out. The current treatment for periodontitis is a deep cleaning of the tooth roots or surgery.

While the idea of developing something that reduces the need for people to visit the dentist for deep cleaning treatments is unquestionably attractive, Guo, one of the first authors on the paper, said she was also thinking about pets.

“My cat, she has periodontal problems,” said Guo. “So I have to bring her to the lab every year to just do the dental cleaning.”

But, she added, “It’s really hard because you have to put the cat into general anesthesia to perform the cleaning. Think about if the owner can just apply the gel at home to their pets.”

The Institute for Systems Biology team took second place for work led by James Heath, president of the institute and a professor there. The long Covid-19 study grew out of research in Heath’s oncology lab, which had developed a pipeline for examining blood and tissue samples. The pandemic hit early in Seattle, and the research team decided to pivot.

“Almost at the very beginning of the pandemic, we had launched a really big study and then we followed patients over time, which it turns out not many people did,” he said, adding, “We began to understand that our patients were not necessarily recovering, and so we set out to better understand what was different about these patients, trying to understand what was different about their disease journeys.”

This led to one of the largest studies to date of biomarkers in long Covid patients. Heath’s team and a host of international collaborators found four factors that help predict which patients will get long Covid: type 2 diabetes, SARS-CoV-2 RNA or Epstein-Barr virus in a patient’s bloodstream, and the presence of specific antibodies, called autoantibodies, that attack the body instead of invaders. The researchers also found that specific biomarkers correlated with specific symptoms, suggesting potential treatments, such as antiviral drugs.

The team was at first stymied by where to look for biomarkers; they collected the usual assays for proteins and metabolites, but the data didn’t tell them anything, Heath said. But colleagues “in the transplant world”  reminded him that “during some immunological events you can reactivate latent viruses,” he said.

When the team started looking for those types of viruses, they observed signals for both latent viruses and autoantibodies. Autoantibodies are present in autoimmune diseases, and thinking about pre-existing conditions and other chronic diseases “brought the whole story together,” Heath said.

Having symptoms after the acute phase of a virus isn’t unusual. However, the large number of people with post-Covid symptoms has opened an opportunity to study the phenomenon at scale, as with the National Institutes of Health’s RECOVER study, for which ISB is the project leader in the Pacific Northwest region. Heath said he is optimistic that long Covid research will help unlock avenues to better understand other chronic diseases no one understands, like post-acute Lyme disease.

“Our medical system is really, really good at looking at acute disease or a broken bone or a tumor that they see on an MRI or a PET scan, but they’re awful at understanding chronic disease,” said Heath, who as a graduate student worked on the spherical carbon allotrope called buckminsterfullerene (the molecules are more affectionately known as “buckyballs”), that won the 1996 Nobel Prize for his advisor and collaborators.

He added, “And so I think that’s actually the major modern medical challenge, is how do you understand chronic disease and how do you do something about it?”

Selected STAT Madness teams will be invited to the STAT 2023 Breakthrough Summit in San Francisco on May 3 and 4. A party will also be held on May 3 for past and present STAT Madness competitors.