By Danielle 
With no U.S. Food and Drug Administration–approved treatments for Sjögren’s disease, which affects about 4 million people in the United States—predominantly women—the National Institutes of Health (NIH) has renewed a $2.1-million grant for a University at Buffalo dental professor, the university says.
The autoimmune disorder, marked by severely reduced tear and saliva production, leaves patients with dry, “cotton-filled” mouths and often causes tooth decay and difficulty swallowing.
“There are no FDA-approved drugs for Sjögren’s other than those that reduce eye inflammation,” said Jill M. Kramer, DDS, PhD, associate professor in the Department of Oral Biology at UB’s School of Dental Medicine. “We don’t have anything that prevents the loss of salivary flow or reverses it. As dentists, we advise patients to drink lots of water, avoid sugary and sticky foods, brush frequently, and use high-fluoride products to manage symptoms and prevent decay.”
Kramer recently received a $2.1-million, five-year renewal grant from the National Institute of Dental and Craniofacial Research (NIDCR), part of the NIH, to continue studying MyD88, a key molecule in the immune system, and how it is activated by various receptors. Her team has been investigating MyD88 since 2017.
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“We know that MyD88 plays a key role in the immune system by helping cells respond to signals that trigger inflammation,” Kramer said. “If you don’t have this molecule, you’re very susceptible to disease.”
In earlier studies, mice prone to Sjögren’s disease had MyD88 genetically removed. These mice did not show the typical dry mouth or inflamed organs, although they often became very sick by six months of age, highlighting that blocking MyD88 may not be a viable therapy for humans.
“Our hope is that by understanding how the disease progresses and how these molecules interact, we can block key mediators of inflammation without compromising patients’ immune systems.”
Kramer and her team, including colleague Rose-Anne Romano, PhD, associate professor of Oral Biology, as well as PhD student Sheta Biswas and master’s student Bayan Alhaddad, are expanding their study to examine specific receptors that activate MyD88 and how they interact in both patients and mice.
Toll-like receptors (TLRs), molecules that help the immune system detect germs or danger, are central to their work. The researchers have identified TLR7 and TLR9 as particularly important and have observed sex-specific differences. Female mice lacking TLR7 showed reduced disease severity, while males became sicker.
“It raises interesting questions about whether males and females might benefit from different treatments,” Kramer said.
Insights from Sjögren’s research could also benefit patients with other autoimmune diseases, such as lupus and rheumatoid arthritis. Studies of TLR7 in lupus models inspired the team’s current approach, showing that similar molecular mechanisms may underlie different conditions.
Kramer emphasized that molecular studies could help classify patients into subgroups, enabling targeted therapies based on specific disease pathways. The team is also working with Jennifer Frustino, DDS, PhD, at Erie County Medical Center to obtain healthy salivary gland tissue, improving understanding of MyD88’s role in inflammation.
“Our hope is that by understanding how the disease progresses and how these molecules interact, we can block key mediators of inflammation without compromising patients’ immune systems,” Kramer said.