Although the complement system is part of the innate immune system, it can cause damage to the body in some cases. Indeed, adverse complement activation contributes to many autoimmune and chronic inflammatory diseases. Now, researchers have described the molecular details of a recently approved class of drugs that can inhibit the complement system. These findings pave the way for further optimization of these inhibitors.
The complement system defends the body against microbial intruders, but it can also attack the body’s own cells for various reasons and thus contribute to clinical complications. These complications range from chronic and age-related inflammatory diseases such as macular degeneration to organ transplant rejection. In such cases, it would make medical sense to shut down the complement system in a controlled manner with the use of drugs.
Despite the wide range of medical applications, there has long been only one class of substances, the “complement inhibitors”, which are only approved for a few very rare diseases anyway. It wasn’t until 2021 that a new treatment option hit the market in the form of compstatins, a class of drugs that immobilizes a central factor in the complement system. The discovery and development of this family of substances is rooted in the research of Professor John Lambris’ group at the University of Pennsylvania, USA.
Now, a research group led by Professor Daniel Ricklin of the University of Basel has worked with Lambris and an international team of researchers to study in detail the mode of action of these compstatins. Write in the journal Nature Communicationthe researchers describe how different variants of this family of active substances interact with the central factor of the complement system and how they work precisely at the molecular level.
Optimize active substances and facilitate research
On the one hand, the results open the way to further optimization of the active substances of the compstatin family. “On the other hand, the results also help us understand why compstatins have a very specific effect on the human complement system,” says Ricklin.
What is beneficial in therapy can turn out to be an obstacle to fundamental research because it prevents working with model organisms. With this in mind, an interdisciplinary research project of the Department of Pharmaceutical Sciences aims to provide clinical research with new variants of the inhibitor that can help to better understand various diseases and open the way to new therapeutic strategies.