Immunotherapy for gum disease? A study in mice is promising

Targeting the immune system could prevent or treat periodontal disease (PD), a common but serious gum disease, according to a new study from the University of Pittsburgh.

The study, published in Proceedings of the National Academy of Sciencesshowed that delivery of microparticles containing the immunomodulatory compound CCL2 directly to the gums inhibited bone loss and accelerated bone repair in a mouse model of PD.

“Treatment for Parkinson’s disease has always focused on targeting bacteria, but bacteria do not actually cause the disease. Rather, they trigger Parkinson’s disease by activating the immune system, leading to inflammation and loss bone around the teeth,” said lead author Charles Sfeir, DDS. , Ph.D., associate professor and chair of the department of periodontics and preventive dentistry at the Pitt School of Dental Medicine and member of the McGowan Institute for Regenerative Medicine. “Our study shows that it’s a two-way street: If we contain the immune system, we can change the composition of the bacteria and prevent the disease from occurring or stop its progression.”

Sfeir teamed up with Steven Little, Ph.D, distinguished professor and chair of the Department of Chemical and Petroleum Engineering in the Swanson School of Engineering and McGowan Fellow, who developed microparticles that provide sustained release of CCL2.

“The potential for engineered systems to interact with the immune system in the periodontal space is enormous and represents a completely different way of treating disease than what is done in the clinic currently,” Little said. “This collaboration with Dr. Sfeir is further proof of the exciting future of this type of technology.”

Led by first author Mostafa Shehabeldin, MS, Ph.D., a graduate student in Sfeir’s lab and now an assistant professor of periodontics at UT Health San Antonio, the researchers first induced Parkinson’s disease in mice by tying a silk thread around it. one of their molars. Floss quickly accumulates bacteria, causing inflammation that begins to rapidly destroy the bone around the teeth in just four days.

To see if CCL2 could prevent Parkinson’s disease or treat an actively progressing disease, the researchers treated the animals with the microparticles at the same time as silk placement or four days afterward. They also examined whether CCL2 would impact self-resolving disease by treating mice with microparticles at the same time as they removed silk.

In all three scenarios, CCL2 therapy helped prevent or treat PD by reducing bone loss and improving bone repair.

This beneficial effect is due to changes in macrophages, the white blood cells that kill microorganisms, remove dead cells and stimulate other immune cells. In PD, most macrophages are of the inflammatory M1 type, but CCL2 treatment shifted them to the anti-inflammatory M2 type.

Microparticle injection also altered the oral microbiome, reducing or preventing increases in overall bacterial load and abundance of certain bacterial species associated with PD.

“PD is an extremely common inflammatory disease that affects many patients with varying degrees of severity,” Sfeir said. “This research is exciting because it has the potential to impact a very large number of people.”

According to Sfeir, who hopes to test this new approach to treating PD in a future clinical trial, CCL2 therapy would likely be developed as an adjunct treatment that would work alongside traditional bacteria-targeting therapies that include regular dental cleanings and antimicrobials.

“For 70 to 80 percent of the population with PD, they get a dental cleaning and the inflammation goes away,” Sfeir said. “But a small fraction of patients, even if they perform regular cleanings and maintain meticulous oral hygiene, still experience bone destruction. For this aggressive Parkinson’s disease, we do not yet have a good therapy. “That’s where we think modulating the immune system with something like CCL2 would be really helpful.”

The results also offer new insights into understanding the interactions between the immune system and the microbiome.

“The oral cavity is one of the few areas of the human body where interactions between microbes and the immune system can be studied, and it is much more accessible than other areas such as the intestine and lungs,” Sfeir said. “This makes Parkinson’s disease a very important model system for other diseases caused by the immune system.”

Other study authors were Jin Gao, Ph.D., Yejin Cho, Rong Chong, MS, Tracy Tabib, MS, Sarah Gaffen, Ph.D., and Robert Lafyatis, MD, all of Pitt; and Lu Li, Ph.D., Matthew Smardz, Patricia Diaz, Ph.D., DDS, all of the University at Buffalo.