Targeting senescent cells may help control and potentially reverse periodontal disease, according to Dr. Sinem Esra Sahingul, senior author of a paper on the new drug therapy.
Senescent cells are known to secrete pro-inflammatory molecules that damage surrounding tissues, impede healing, and accelerate disease progression. Previous research by the Penn Dental School team has shown that chronic periodontitis may even induce cellular senescence in younger tissues.
Building on this, a new translational study led by Dr. Sinem Esra Sahingul, Associate Professor in the Department of Periodontology and Associate Dean for Graduate Education and Student Research at the University of Pennsylvania Dental School, explores how targeting senescent cells can help manage periodontitis.
“Our findings suggest that senescent cell therapy offers a promising approach to maintaining periodontal health,” Dr. Sahingul said in a press release.
Periodontitis is not just a bacterial infection, it is driven by immune and metabolic dysfunction, cellular senescence, and inflammation.
By targeting inflammation and senescent cells, we may break the chronic disease cycle and unlock new preventive and therapeutic possibilities for oral and systemic health.”
The study tested a combination therapy using dasatinib, a drug that helps clear senescent cells by inhibiting an enzyme that is essential for their survival, and quercetin, a natural flavonoid widely available as an over-the-counter supplement.
Previous studies have shown that this combination reduces senescent cell burden and associated markers in other disease settings.
The in vitro experiments involved exposing human gingival keratinocytes to periodontitis-associated bacteria to induce senescence-associated cellular changes. Treatment with dasatinib and quercetin significantly reduced markers of senescence and associated periodontal inflammation and bone loss.
Similar results were observed in vivo, with gingival tissue from the animal model showing reduced senescence and inflammation, with tissue characteristics restored to levels seen in young healthy controls.
Notably, the treatment also helped prevent alveolar bone loss, suggesting a potential role in maintaining the structural integrity of periodontal tissues.
Dr. Sahingul noted: “These results are consistent with our previous studies and a growing body of research that suggests natural compounds such as quercetin have a powerful role in promoting oral and systemic health.”
The research team now plans to initiate an early clinical trial to evaluate the effects of quercetin on clinical and biomarker outcomes in patients with periodontitis.
Future trials may also investigate low-dose, intermittent use of dasatinib, currently approved for the treatment of leukemia, to assess its safety and efficacy in the treatment of periodontal disease.
Dr. Sahingul said: “We hope that these initial clinical trials will provide proof-of-concept for harnessing the therapeutic potential of natural products – either as stand-alone agents or in combination regimens – as host modulation strategies to improve clinical outcomes in periodontitis management.
If successful, this could lay the foundation for more targeted and effective treatments and dosing regimens, particularly for patients at high risk for severe periodontal disease, such as the elderly, diabetics, and immunocompromised individuals.”
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