Targeted pharmacological agents for the prevention of multiple organ failure in hemorrhagic shock patients

This technology is a pharmacological intervention targeting localized inflammatory responses in trauma and hemorrhagic shock to prevent multiple organ failure.

Unmet Need: Addressing inflammation and metabolic stress in hemorrhagic shock

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 multiple organ failure (MOF) in survivors. Such approaches do not adequately address the 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: Pharmacological agent-based therapy for multiple organ failure prevention

This technology employs a strategic approach to enhance recovery from T/HS by utilizing the protective mechanisms of CD39 and CD73. These molecules 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 targeting these molecules, the technology aims to localize the beneficial effects of adenosine production within areas of inflammation, avoiding the systemic effects that direct adenosine receptor activation could cause. Early findings from animal models have shown that interventions such as the administration of CD39 mimic apyrase and recombinant CD73 can significantly reduce lung and liver injury indicators, including lung permeability and neutrophil infiltration, as well as liver enzyme levels. 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
• Cancer immunotherapy
• Improving organ transplant outcomes
• Treatment of hyperinflammatory conditions

Advantages:

• Localized effectiveness
• Enhanced patient recovery
• Reduced organ damage
• Direct prevention and treatment of shock-induced multiple organ failure

Lead Inventor:

George Hasko, Ph.D.

Patent Information:

Patent Pending

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. 2023 Sep 26: 10.1097.

• 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