Diagnosis and treatment of periodontitis

Due to the large numbers of individuals affected by periodontitis, the lack of targeted strategies to predict and prevent this disease represents a huge gap in the healthcare product market and constitutes a substantial part of the total treatment costs of 10 billion SEK per year. The incidence of periodontitis and associated diseases is expected to rise significantly due to growing numbers of elderly patients with natural teeth and the increased use of dental implant treatment over the past 15 years. Periodontitis is an oral disease characterized by destruction of tooth-supporting tissues and is the most common inflammatory disorder of humans. Porphyromonas gingivalis is considered to play a major causative role in the etiology of periodontal disease, mainly by expressing a high proteolytic activity through gingipains. Frequent periodontitis-induced bacteraemias involving P. gingivalis and their gingipains may contribute to systemic inflammatory conditions leading to e.g., cardiovascular and Alzheimers disease. In accordance, we have reported that gingipains in vitro modify LDL by cleaving apoB 100 and that patients with periodontitis express an atherogenic form of LDL.

Periodontal diagnosis and treatment as of today is very traditional and conventional and has been carried out with the same strategies and guidelines for many decades. Although these techniques are easy to implement, there is a need for new innovative strategies. Probing pocket depth is not a standardized method and can differ between individual clinicians, and radiological assessment varies a lot, making it hard to compare the progression of marginal bone loss over time. Some sort of biosensor technology for periodontal detection would be of great value for many reasons. This technique would enable early detection of the disease which could stop many years of suffering for the patients. Regarding new treatments for periodontal disease, antibacterial peptides seem very promising. We have recently reported that a specific bacteriocin, PLNC8ab, efficiently inhibits and kills P. gingivalis, suggesting that this peptide can be used in the prevention and treatment of periodontitis and associated systemic disorders.

The overall aim of this project is to develop and evaluate novel diagnostic and therapeutic strategies for periodontitis. More specifically, the objectives are to develop different strategies with gold nanoparticle-based biosensors that measures proteolytic activity, for rapid diagnosis of periodontal disease, and to test the function of these biosensors in vitro and in clinical samples. Furthermore, to evaluate the antibacterial effects of bacteriocin PLNC8ab or its derivates, as therapeutic agents in the inhibition of P. gingivalis in patients with periodontitis.

Articles

• Zhang B, Khalaf H, Sirsjö A, Bengtsson T. (2015). Gingipains from the periodontal pathogen Porphyromonas gingivalis play a significant role in regulation of Angiopoietin 1 and Angiopoietin 2 in human aortic smooth muscle cells. Infect. Immun. 83(11):4256-65.
• Khalaf H, Lönn J, Bengtsson T. (2014). Cytokines and chemokines are differentially expressed in patients with periodontitis: Possible role for TGF-β1 as a marker for disease progression. Cytokine. 67(1):29-35.