Developing a Novel Treatment for Systemic Inflammation

Miguel Cruz - High Res (320x240)
Dr. Miguel Cruz, Department of Medicine, Division of Thrombosis

Dr. Miguel Cruz, an associate professor in the Department of Medicine at Baylor College of Medicine, Thrombosis Division, has devoted his research efforts to developing a treatment for systemic inflammation (i.e., endotoxemia, sepsis).

Sepsis is a systemic inflammatory response to an infection or insult. Severe sepsis is a serious public health concern in the United States. It is a common diagnosis among critically ill patients and carries a high mortality rate. However, the pathophysiology of sepsis is not well understood, and afflicted patients deteriorate rapidly as a result of the progressive failure of multiple organs. In sepsis, hyperactivation of the immune response leads to the excessive production of various pro inflammatory cytokines and cellular injury.

Sepsis can be caused by a non-infectious or infectious insult, including Lypolysaccharide (LPS or endotoxin). LPS is a component of the outer cell membrane of Gram-negative bacteria that can initiate a parallel cascade of events that contribute to the clinical manifestations of sepsis.

Dr. Cruz has shown efficacy of the isolated A2 domain of the von Willebrand Factor (VWF) in improving survival of mice with lethal LPS-induced endotoxemia. The animal model closely models microvascular thrombosis and associated organ failure seen with sepsis. The pretreated animals became sick but none died compared to the controls. In vitro, Dr. Cruz has observed that purified A2 peptide inhibits VWF mediated platelet adhesion to fibrin, which suggests that A2 peptide prevents thrombus formation.

A patent based on Dr. Cruz’s discovery, titled “Treatment of Medical Condition With A2 Domain of Von Willebrand Factor,” has been issued to Baylor College of Medicine. Dr. Cruz is continuing research on A2 peptide in efforts to reduce the morbidity and mortality associated with clinical conditions generally caused by endotoxin or bacterial products and has been awarded funding from the Alkek Award for Pilot Projects in Experimental Therapeutics to continue the effort towards clinical application.

Applications/Advantages

  • Administration of the A2 peptide was associated with a dramatic, complete reduction in sepsis-associated mortality in animal models.
  • This novel therapy has applications in sepsis and inflammation resulting from either an infectious or non-infectious insult.
  • The A2 peptide therapeutic molecule presents low immunogenicity and a low hurdle to tolerance.
  • Additional ongoing work will examine the mechanism and consequences of administration of the A2 peptide on a panel of biomarkers associated with systemic inflammation in humans.

BLG Project Manager

Mercy Chen, Ph.D. (mschen@bcm.edu)