The medicine of the future against infection and inflammation?

Researchers at Lund University in Sweden, have in collaboration with colleagues in Copenhagen and Singapore, mapped how the body's own peptides act to reduce infection and inflammation by deactivating the toxic substances formed in the process. The study is published in Nature Communications and the researchers believe their discovery could lead to new drugs against infection and inflammation, for example in wound healing.

The toxins that are neutralised, known as lipopolysaccharides (LPS), come from the bacterial cell walls and generate an inflammatory reaction. The reaction is a necessary part of our immune defence system in which our bodies respond quickly and fight invasive bacteria. However, it can be over-activated and become harmful, as observed in infected skin wounds, infections in various organs, or in the case of bacteria spreading to the blood, which can lead to sepsis.

"We know from previous studies what the task of these peptides is but now we have mapped how they proceed in gradually reducing an inflammatory reaction", says Artur Schmidtchen, professor of dermatology and venereology at Lund University and consultant physician at Skåne University Hospital in Lund.

"By use of advanced biophysics such as nuclear magnetic resonance analysis, combined with molecular modelling and biological studies we show that these peptides form a C-shaped structure which enables the capturing and inactivation of LPS. They also simultaneously interfere with receptor-mediated inflammatory responses", adds Rathi Saravanan, senior research fellow at Lee Kong Chian School of Medicine at Nanyang Technological University, Singapore, and first author of the study.

"Currently, most drugs aim to more or less completely block a target, such as a receptor. But that risks a deactivation of the immune defence system which can be detrimental and downright dangerous. The body's own defence mechanisms proceed with greater caution in what is known as a transient manner: the peptides act on their target for a short time to reduce an inflammation towards normalisation. It is the natural functions of these peptides that we want to develop into new drugs", says Artur Schmidtchen, who has been researching the field of innate immunity for over 20 years.

In addition, the peptides present in thrombin, a common blood protein, are multifunctional and can attack several targets, unlike current drugs.

The dermatology researchers now want to develop a peptide gel for improved wound healing in patient studies.

"That is the primary goal, but we will also be looking at the possibility of developing new drugs against infections in the eyes and various internal organs. This will become a new way of preventing both infection and inflammation without using antibiotics."

Rathi Saravanan, Daniel A Holdbrook, Jitka Petrlova, Shalini Singh, Nils A Berglund, Yeu Khai Choong, Sven Kjellström, Peter J Bond, Martin Malmsten, Artur Schmidtchen.
Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides.
Nature Communicationsvolume 9, Article number: 2762. doi: 10.1038/s41467-018-05242-0.

Most Popular Now

Novartis receives FDA approval for Mayzent® (sipon…

Novartis today announced that the US Food and Drug Administration (FDA) has approved Mayzent® (siponimod) for the treatment of adults with relapsing forms of multiple scl...

First bacterial genome created entirely with a com…

All the genome sequences of organisms known throughout the world are stored in a database belonging to the National Center for Biotechnology Information in the United Sta...

Clinical trial finds therapy to be well-tolerated …

A phase I clinical trial that set out to assess the safety of a new combination therapy for a type of aggressive brain tumour has found the treatment to be well tolerated...

Liver, colon cancer cells thwarted by compounds de…

The plant that adds flavor, color and bitterness to beer also produces a primary compound that thwarts cancer cells, and two important derivatives of the compound do as w...

Compound that kills drug-resistant fungi is isolat…

Antimicrobial and antifungal resistance, which describe the ability of bacteria and other pathogens to resist the effects of drugs to which they were once sensitive, is a...

Boehringer Ingelheim announces FDA and EMA regulat…

Boehringer Ingelheim has filed for regulatory approval of nintedanib in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD) with the FDA and E...

Selumetinib granted US Breakthrough Therapy Design…

AstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that the US Food and Drug Administration (FDA) ha...

FDA approves treatment for patients with a type of…

The U.S. Food and Drug Administration today approved Cimzia (certolizumab pegol) injection for treatment of adults with a certain type of inflammatory arthritis called no...

Novartis adds clinical and preclinical anti-inflam…

Novartis announced that it is adding to its broad portfolio of immunomodulatory medicines with the planned acquisition of IFM Tre, a subsidiary of IFM Therapeutics LLC fo...

Forxiga approved in Japan for type-1 diabetes

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Forxiga (dapagliflozin) as an oral adjunct treatment to insulin for adults with type-1 diabetes (T...

Immune cells fighting blood cancer visualized for …

When cancer escapes the immune system, our defenses are rendered powerless and are unable to fight against the disease. Chimeric antigen receptor T cells (CAR T cells) re...

Bayer reaches settlement to resolve Xarelto™ litig…

More than five years after the Xarelto™ litigation began, and with Bayer and Janssen Pharmaceuticals prevailing in all six cases that went to trial, the companies have re...