Prevent antibiotic resistance and preserving the natural microbiome

Innovative therapeutic approaches to treat periodontitis are being developed by PerioTrap Pharmaceuticals GmbH, Skinomics GmbH, the Fraunhofer Institute for Cell Therapy and Immunology IZI and the Fraunhofer Institute for Microstructure of Materials and Systems IMWS in the joint project "Paropaste". They are focusing on blocking the germs responsible for this rather than killing them. This approach, which could help prevent antibiotic resistance, will be presented by the research consortium from Halle (Saale) at the IADR/AADOCR/CADR General Session in New Orleans, USA, on March 14, 2024.

© TGZ Halle GmbH / Marco Warmuth
Periodontitis affects half of the adult German population. Severe cases are currently treated with antibiotics.

Periodontitis is a widespread disease: half of the adult German population is affected by this chronic inflammatory disease of the periodontium, which is usually caused by a disruption of the bacterial balance in the oral cavity and on the teeth. The consequences are by no means limited to toothache, bleeding gums or tooth loss. The constant inflammation and the migration of pathogenic germs into the human body promote diseases such as diabetes, rheumatism, Alzheimer's and chronic inflammatory bowel disease. Because antibiotics are also used to treat severe cases of periodontitis in particular, the high number of cases of the disease also contributes to the spread of antibiotic resistance and the emergence of multi-resistant germs, which kill more than one million people worldwide every year.

"In severe cases of periodontitis, antibiotics are intended to eliminate the bacterial biofilm in gum pockets. However, when tablets are administered, the medication affects the entire body. Many beneficial bacteria in places other than the oral cavity come into contact with the active ingredient and are killed, resulting in an unnecessarily high risk of resistance developing," explains Dr. Andreas Kiesow, Group Leader "Characterization of medical and cosmetic care products" at the Fraunhofer IMWS.

In the joint project "Paropaste", which is being funded by the Federal Ministry of Education and Research (BMBF) with a total of 3 million euros as part of the "KMU-innovativ: Biomedicine" funding program, the project partners are therefore focusing on an alternative approach to inhibiting the disease-causing bacteria: They want to use a special active substance, which is applied directly to the oral cavity, to inhibit an enzyme that occurs almost exclusively in the bacteria that cause periodontitis. Without the effect of this enzyme, the bacteria can no longer produce several so-called virulence factors and therefore ultimately no longer cause disease in humans. "While classic antibiotics inhibit the basic growth of all good and bad germs, we only want to take the dangerous bacteria out of play in their pathogenic effect. In this way, the natural microbiome in the oral cavity can be preserved or restored instead of destroying the entire germ spectrum," says Dr. Mirko Buchholz from PerioTrap, scientific director and co-founder of the company.

The four project partners, who are all based at the Weinberg Campus in Halle (Saale), will present the approach on March 14 at the "2024 IADR / AADOCR / CADR General Session" in New Orleans, USA, in the lecture "A new approach for re-balancing the oral microbiome" and with two poster contributions. The four-day conference is organized by the International Association for Dental, Oral, and Craniofacial Research (IADR), the American Association for Dental, Oral, and Craniofacial Research (AADOCR) and the Canadian Association for Dental Research (CADR). It is one of the largest scientific conferences of its kind in the world.

In the "Paropaste" project, the Fraunhofer IMWS is primarily contributing its many years of experience in materials science for innovative dental care and oral care applications. Among other things, the project is investigating whether the locally applicable formulation created in the project interacts with dental tissue in the desired way and is compatible with humans.

The Fraunhofer IZI, where the innovative treatment approach was generated and whose spin-off is PerioTrap GmbH, develops and validates the bioanalytical methods for characterizing the drug candidates and conducts experiments on drug transport, local bioavailability and toxicity. Skinomics is responsible for the selection, characterization and testing of a suitable galenic carrier system for selected drug candidates in the project as well as regulatory work on clinical evaluation and scaling-up processes.

If the project partners are successful and can demonstrate the potential effectiveness of the approach, "Paropaste" will be tested in clinical trials. Around 20 million patients in Germany alone could then benefit from an effective new therapeutic approach every year.