IIt started with mouse molars and a humpback.
The New York University College of Dentistry team that won the 2023 STAT Madness competition has 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 composition of bacteria found in the mouth.
“We were happy because we think that ultimately, hopefully this treatment will benefit a lot of people,” said Yuqi Guo, a research associate at NYU and one of the study’s two lead authors.
STAT’s month-long, armband-style celebration of biomedical research garnered 145,244 votes for studies on topics ranging from bacteria-resistant catheters to brain-changing fungi to robotic drug-delivering mucus-cleansing capsules. In the end, the NYU team studying gum disease, with 57% of the votes in the final ranking, beat out a team from the Institute for Systems Biology in Seattle that studied ways to predict who will develop long-term Covid.
The NYU team used mice to model periodontitis, a bacterial infection that causes gum inflammation. The researchers slipped a suture thread into a loop around the molars of mice to mimic the irritation caused by food stuck to human teeth. To mimic the long-term disease, some mice had their gums primed 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, may feed 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 reduced the symptoms of periodontitis.
The study was published in the journal Cell Reports in September 2022. The authors are currently receiving approvals for further testing before moving to human trials.
More than 47% of US adults over the age of 30 have some form of periodontal disease, according to the Centers for Disease Control. In early stage gingivitis, known as gingivitis, the gums may become swollen and red and may bleed. If not corrected with daily flossing and brushing to remove bacteria in plaque—and regular cleanings to remove tartar—gingivitis can progress to periodontitis, in which the gums can recede from the teeth and bone can be lost. , causing the teeth to fall out. Current treatment for periodontitis is deep root cleaning or surgery.
While the idea of developing something that reduces the need for people to visit the dentist for deep-cleaning treatments is undeniably appealing, Guo, one of the paper’s first authors, said she was also thinking about pets.
“My cat has periodontal problems,” Guo said. “So I have to bring her to the lab every year to just get the dental cleaning done.”
But, he added, “it’s really difficult because you have to put the cat under general anesthesia to do the cleaning. Consider if the owner can simply 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 lengthy Covid-19 study grew out of research in Heath’s oncology laboratory, which had developed a pipeline to test blood and tissue samples. The pandemic hit Seattle early and the research team decided to pivot.
“Almost at the beginning of the pandemic, we had started a really big study and then we were following patients over time, which it turns out not many people were doing,” he said, adding, “We started to understand that our patients weren’t necessarily recovering and so we set out to better understand what was different in these patients, trying to understand what was different in their disease journeys.”
This led to one of the largest biomarker studies to date in long-term Covid patients. Heath’s team and a host of international collaborators found four factors that help predict which patients will be sick for a long time: type 2 diabetes, SARS-CoV-2 or Epstein-Barr virus RNA in a patient’s bloodstream, and the presence of specific antibodies , called autoantibodies. , which attack the body instead of invaders. The researchers also found that specific biomarkers correlated with specific symptoms, pointing to potential treatments, such as antiviral drugs.
The team at first balked at where to look for biomarkers. They collected the usual analyzes for proteins and metabolites, but the data told them nothing, Heath said. But colleagues “in the transplant world” reminded him that “during certain immune events you can reactivate latent viruses,” he said.
When the team started looking for these types of viruses, they noticed signals for both latent viruses and autoantibodies. Autoantibodies are present in autoimmune diseases, and thinking about preexisting conditions and other chronic diseases “tied the whole story together,” Heath said.
Having symptoms after the acute phase of a virus is not unusual. However, the large number of people with post-Covid symptoms has opened up an opportunity to study the phenomenon at scale, such as with the National Institutes of Health’s RECOVER study, for which ISB is the Pacific Northwest region project leader. Heath said he is optimistic that the lengthy research into Covid will help open avenues to better understanding other chronic diseases that no one understands, such as post-acute Lyme disease.
“Our medical system is really, really good at looking at acute disease or a broken bone or a tumor they see on an MRI or a PET scan, but it’s terrible at understanding chronic disease,” said Heath, who as a graduate student worked in the spherical allotrope of carbon called buckminsterfullerene (the molecules are better known as “buckyballs”), which won the 1996 Nobel Prize for his advisor and collaborators.
He added, “And so I think that’s actually the biggest 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 3rd and 4th. A party will also be held on May 3rd for past and current STAT Madness contestants.
