22 April 2022

Anti-inflammatory nanoteles

Alpaca antibodies can treat the root cause of chronic inflammation

Svetlana Maslova, Hi-tech+

First, scientists determined the mechanism of development of chronic inflammation, and then showed how it can be suppressed in the embryo with the help of fragments of alpaca antibodies. In preclinical models, experimental treatment has already led to a reduction in the symptoms of rheumatism and gout.

Scientists from Germany and Brazil have found a new approach to the treatment of chronic inflammation, which provokes numerous incurable diseases in humans from arthritis to dementia. They showed that with the help of mini-antibodies with a simple structure, it is possible to fight the root cause of this condition, it is reported  on the website of the University of Bonn.

Article by Bertheloot et al. Nanobodies dismantle post-pyroptotic ASC specks and counteract inflammation in vivo is published in the journal EMBO Molecular Medicine – VM.

Our cells have a complex signaling system — the inflammasome, the central component of which is the ASC protein. In case of danger, for example, when a pathogen is attacked, ASC forms clusters that lead to two consequences. First, the cell begins to accumulate a large amount of messenger substances necessary to activate the immune response. Secondly, pores are formed in the cell membrane through which these signaling molecules can be released outside and carry out their function.

Now scientists have discovered that ASC accumulations can accumulate in tissues for a long time, provoking continuous activity of the immune system. This leads to chronic inflammation.

Understanding the root cause of the condition, researchers began to look for new treatment strategies. To do this, they turned to alpacas for help: the animals were injected with ASC to produce simple-structured antibodies, fragments of which were used in the treatment of chronic inflammation in laboratory mice.

"Nanobodies are very small compared to conventional antibodies, so they are excellent for destroying such molecular complexes. And unlike antibodies, they cannot provoke additional stimulation of the immune system and, thereby, worsen inflammation," the authors explained.

In rodents, treatment led to a significant reduction in the symptoms of rheumatism and gout, and in human cell culture, scientists recorded the dissolution of ASC accumulations.

alpaka.jpg

When infected cells (purple) burst, they secrete clusters of ASC (light blue). Nanoteles (yellow) ensure their splitting.

Now the researchers plan to test the experimental therapy on dementia models, since it is known that ASC clusters can serve as an impetus for the spread of beta-amyloid proteins in brain tissue. In the future, the effectiveness of this strategy will be tested on various diseases with characteristic chronic inflammation, which will allow us to assess its versatility and potential for humans.

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