University of Pennsylvania

The Brigham and Women's Hospital, Inc.

Robert Bucki

Thomas P Stossel

Paul A Janmey

Scott L Diamond

David E Fein

Richard Chaby

Thomas P Hematology Division Stossel

Provided are methods of using gelsolin and active fragments thereof to neutralize, treat or prevent the pathogenic effects of lipoteichoic acid (LTA) toxins released from gram-positive bacteria, including massive activation of inflammatory response in a patient and the resulting lethal septic shock. The provided gelsolin binds to and neutralizes LTA from various bacteria, as well as eukaryotic acidic lysolipids adversely associated with bacterial sepsis and inflammation in the patient, with high affinity, thereby decreasing circulating LTA and the eukaryotic markers, and negating the deleterious biological effects of the gram-positive bacterial infection. Consequently, the provided gelsolin replacement therapy offers a method and compositions for the prevention of bacterial sepsis-induced mortality in the patient.

Methods of using gelsolin to treat or prevent bacterial sepsis

The invention relates generally to antimicrobial cationic steroid pharmaceutical compositions, methods of making antimicrobial cationic steroid pharmaceutical compositions, and methods of using antimicrobial cationic steroid pharmaceutical compositions.

Antimicrobial cationic steroids and methods of use

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Philadelphia, PA, United States of America

Robert Bucki