Prevention, therapy and prognosis/monitoring in sepsis and septic shock

Abstract

The invention relates to the use of a peptide which binds to lipopolysaccharide (LPS) or lipoteichoic acid (LTA), for manufacturing a pharmaceutical composition for treating sepsis or septic shock, wherein the peptide comprises the amino acid sequence of apolipoprotein CI (apoCI) or a part thereof that comprises at least the amino acids of the C-terminal helix of apoCI. The use of human apoCI is preferred. The peptide can be administered clinically to patients who have sepsis or threaten to develop sepsis. Measurement of the apoCI content in blood can be utilized for determining the severity and prognosis of the course of the septic condition or for monitoring an anti-sepsis treatment.

1 . A pharmaceutical composition for preventing or treating sepsis or septic shock, which composition comprises a peptide floating therein, which method comprises the steps of which binds to a lipopolysaccharide (LPS) or lipoteichoic acid (LTA) wherein the peptide comprises the amino acid sequence of apolipoprotein CI (apoCI) or a part thereof that comprises at least the amino acids of the C-terminal helix of apoCI as well as a pharmaceutically acceptable carrier. 
     
     
         2 . The composition according to  claim 1 , wherein the peptide comprises the amino acid sequence of human apoCI or a part thereof that comprises at least the amino acids of the C-terminal helix of human apoCI. 
     
     
         3 . The composition according to  claim 2 , wherein the peptide is human apoCI or a fragment thereof that comprises at least the amino acids MREWFSETFQKVKEKLK. 
     
     
         4 . The composition according to  claim 3 , wherein the peptide is human apoCI having the amino acid sequence TPDVSSALDKLKEFGNTLEDKARELIS RIKQSELSAKMREWFSETFQKVKEKLKIDS. 
     
     
         5 . A method for treating or preventively treating a mammal, which suffers from or is at increased risk of developing sepsis, wherein to the mammal an active amount is administered of a peptide as defined in  claim 1 . 
     
     
         6 . The method according to  claim 5 , wherein the mammal is a human. 
     
     
         7 . The method according to  claim 5 , wherein the mammal is at increased risk of developing sepsis as a result of a surgical intervention or a weakened immune system. 
     
     
         8 . A method for determining the severity of a septic condition and making a prognosis for the further course of the sepsis or septic shock in a mammal, or for monitoring a treatment of sepsis or septic shock in a mammal, which suffers from sepsis or septic shock, wherein the apoCI content is determined in a blood sample of the mammal. 
     
     
         9 . The method according to  claim 8 , wherein the mammal is a human. 
     
     
         10 . A method of manufacturing a pharmaceutical composition, comprising using a peptide according to  claim 1 . 
     
     
         11 . The method according to  claim 10 , wherein the peptide binds to lipoteichoic acids and wherein the composition is for preventing or treating a sepsis or septic shock in mammals. 
     
     
         12 . The method according to  claim 11 , wherein the shock is caused by Gram-negative bacteria. 
     
     
         13 . The method according to  claim 12 , wherein the mammal is a human, horse, cow, dog or cat. 
     
     
         14 . The method according to  claim 11 , wherein the shock is caused by Gram-positive bacteria. 
     
     
         15 . The method according to  claim 14 , wherein the mammal is a human, horse, cow, dog or cat.