Office of Technology Transfer – University of Michigan

Inhibition of histone modifying enzymes improves survival following trauma and hemorrhagic shock

Technology #6366

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Researchers
Hasan B. Alam
Managed By
Tiefei Dong
Senior Licensing Specialist, Life Sciences 734-763-5332

The leading cause of death in persons under the age of 44 is trauma, with up to 40% of these mortalities associated with hemorrhagic shock. Hemorrhagic shock results from a loss of more than 20% of circulating blood volume. This results in oxygen deprivation in tissues and major organs, which can lead to organ failure and ultimately death. Current treatment of hemorrhagic shock includes replacement of blood volume and blood cells, though additional injury associated with reperfusion is common. Despite the knowledge of the pathophysiology of hemorrhagic shock in trauma patients, the mortality rate remains high and there are no active interventions available.

Peptidylarginine deiminase inhibitor improves survival following hemorrhagic shock

The peptidylarginine deiminase (PAD) family of enzymes plays a vital role in normal physiology and inflammation through citrullination of arginine side chains. It was recently observed that the administration of a PAD inhibitor, YW3-56, led to a significant increase in survival of animals following hemorrhagic shock. The addition of YW3-56 to in vitro mouse macrophage cultures exposed to hypoxic conditions led to an increase in cellular viability and inhibition of pro-inflammatory cytokines. This demonstrates that the administration of YW3-56 significantly improves survival in vivo and in vitro following hemorrhagic shock conditions. YW3-56 presents a unique therapeutic for immediate intervention to reduce mortality in trauma patients.

Applications

  • Therapeutic for hemorrhagic shock

Advantages

  • Specific inhibitor for PAD4
  • Significant increase in survival following hemorrhagic shock