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USE OF BETA-ANTITHROMBIN IN THE TREATMENT OF BACTERIAL INFECTIONS

[Category : - HEALTH]
[Viewed 476 times]

The present invention relates to beta- antithrombin for use in treating life-threatening microbial infections. Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. We identified three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-?B. We found that the modulating effect is primarily restricted to the less abundant ?-isoform (h?AT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of h?AT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or h?AT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. We also found that in a lethal E. coli infection model, survival rates increased when mice were treated with h?AT . The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
Thus, we claim that human antithrombin can be used to treat severe infectious diseases including, sepsis, severe sepsis, and septic shock.

Patent publications:

WO 2020053426

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heikoherwald (Sweden)

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