One step closer to treating serious bacterial infections and sepsis

The development of a new treatment strategy for bacterial infections and sepsis is led by researchers at Lund University. In a study published in Natural communicationsResearchers demonstrate how they can neutralize toxic substances from bacteria by mimicking a substance naturally present in the body and thus alleviate harmful inflammation that could otherwise lead to sepsis.

“Despite decades of research, there is currently no specific treatment for sepsis. Today, drawing inspiration from the body’s peptide-based defense mechanisms, we have developed a new approach to treating bacterial infections serious,” says Artur Schmidtchen, professor of dermatology and venereology and senior consultant at Skåne University Hospital, who led the study.

For more than two decades, Schmidtchen and his research group have studied endogenous peptides, smaller protein fragments found in the body that can both kill bacteria and neutralize bacterial toxins released during infection.

These peptides have also been shown to be powerful tools in managing the harmful inflammatory response that occurs in the body following infection. The functions of peptides are crucial: if infection and inflammation are not controlled, they can lead to sepsis.

By mimicking the natural structure of thrombin protein peptides, researchers designed a peptide-based treatment, sHVF18. It blocks a receptor, CD14, which plays a key role in detecting bacterial substances and triggering the immune response. This response is crucial to fighting infection but can, if overactivated, lead to sepsis. Additionally, the designed structure also blocks various toxins released by bacteria, thereby regulating inflammation.

“We are using what hundreds of millions of years of evolution have developed as a defense against infections when developing this treatment. It is an effective and natural strategy targeting multiple therapeutic targets simultaneously, and The positive results we observe indicate its potential for clinical use.” Schmidtchen said.

Using advanced analytical methods, researchers examined the structure and function of sHVF18 at the cellular level. They also studied the treatment’s effectiveness in preclinical animal models, with promising results on infection and inflammation in mice. In an experimental pig model of systemic inflammation, treatment with sHVF18 resulted in a significant reduction in lung damage, increased blood oxygen levels, and improved kidney function compared to the control group that did not not received treatment.

“Our detailed knowledge of how sHVF18 works at the molecular level and its effects in preclinical animal models is now being used in the development of sHVF18-based therapies against infections and other inflammatory diseases,” says Ganna Petruk, associate professor at Lund University, who, along with Lund University researcher Manoj Puthia, shares first authorship of the current article.

The next step is to advance the project with the aim of developing sHVF18 as a drug.

“There are currently no established treatments that attenuate the harmful inflammation of infections and prevent the onset of sepsis. But before we can administer it to patients, we need to conduct various safety studies, which we have planned. We hope to evaluate our new treatment concept in patients within a few years”, says Artur Schmidtchen.