CD39 and CD73 enzyme mimics for the prevention of multiple organ failure in hemorrhagic shock patients

This technology is a CD39 and/or CD73 enzyme mimic, given alone or in transfused blood products, that targets localized inflammatory responses in trauma and hemorrhagic shock to prevent multiple organ failure and acute respiratory distress syndrome.

Unmet Need: Addressing inflammation and metabolic stress in hemorrhagic shock

Hemorrhagic shock causes an estimated 1.9 million deaths worldwide each year, most of them from physical trauma. The current strategies for managing trauma and hemorrhagic shock (T/HS) primarily aim at symptom management and patient stabilization but fall short in preventing the progression to acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF) in survivors. Such approaches do not adequately address the ischemia-reperfusion injury, localized inflammation, metabolic stress and anoxia that result in MOF, and the absence of FDA-approved therapies specifically targeting these aspects of HS points to a substantial gap in treatment options. Identifying and developing targeted interventions to mitigate the inflammatory responses triggered by HS is crucial to improving patient outcomes.

The Technology: CD39/CD73 enzyme-based therapy for multiple organ failure prevention

This technology enhances recovery from trauma/hemorrhagic shock (T/HS) by administering soluble mimics of CD39 and CD73, such as apyrase or recombinant human CD39 and CD73. These enzymes are critical in converting ATP to adenosine, a compound that accumulates in response to metabolic stress and exhibits anti-inflammatory and protective qualities in shock scenarios. By supplying these enzymes, the technology localizes the beneficial effects of adenosine production within areas of inflammation, avoiding the systemic effects that direct adenosine receptor activation could cause. The mimics can be given systemically or mixed into transfused blood products such as packed red blood cells, whole blood, plasma, or platelets. This suggests a promising avenue for preventing organ failure in patients experiencing trauma and hemorrhagic shock by harnessing the localized anti-inflammatory effects of these molecules.

This technology has been validated in a trauma/hemorrhagic shock (T/HS) mouse model.

Applications:

• Preventative medicine for multiple organ failure and acute respiratory distress syndrome after hemorrhagic shock
• Treatment of trauma-induced hemorrhagic and hypovolemic shock
• Reducing ischemia-reperfusion injury in the lung, liver, heart, and kidney
• Additive for transfused blood products such as packed red blood cells, plasma, and platelets

Advantages:

• Localized effectiveness without the systemic effects of direct adenosine receptor activation
• Compatible with standard blood transfusions during resuscitation
• Reduced organ damage in the lung and liver
• Direct prevention and treatment of shock-induced multiple organ failure

Lead Inventor:

George Hasko, M.D., Ph.D.

Patent Information:

Patent Pending (US 19/363,111)

Related Publications:

• Lovászi M, Németh ZH, Kelestemur T, Sánchez IV, Antonioli L, Pacher P, Wagener G, Haskó G. “Evaluation of components of the extracellular purinergic signaling system in human sepsis.” Shock. 2024 Apr 1; 61(4): 527-540.

• Kelestemur T, Németh ZH, Pacher P, Beesley J, Robson SC, Eltzschig HK, Haskó G. “Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling.” Respir Res. 2023 Jul 13; 24(1):186

• Kelestemur T, Németh ZH, Pacher P, Antonioli L, Haskó G. “A2A adenosine receptors regulate multiple organ failure after hemorrhagic shock in mice.” Shock. 2022 Oct 1; 58(4): 321-331.

• Csóka B, Németh ZH, Törő G, Koscsó B, Kókai E, Robson SC, Enjyoji K, Rolandelli RH, Erdélyi K, Pacher P, Haskó G. “CD39 improves survival in microbial sepsis by attenuating systemic inflammation.” FASEB J. 2015 Jan; 29(1): 25-36.

Tech Ventures Reference:

• IR CU23263

• Licensing Contact: Kristin Neuman