Plasma Gelsolin

BioAegis’ portfolio is built around plasma gelsolin technology and therapeutics for infectious and inflammatory diseases.
plasma-gelsolinPlasma gelsolin (pGSN) is an ancient, highly conserved human protein that is the 4th most abundant plasma protein in healthy individuals. It is a key component of the innate immune system. In healthy individuals its role is to keep inflammation localized to the site of injury and to boost the body’s ability to clear pathogens.

Plasma gelsolin is depleted by the inflammatory response and is highly correlated to the extent of disease or injury. An extensive literature of human studies has shown depletion of pGSN in a diverse set of clinical conditions marked by inflammation, tissue injury and/or infection such as acute respiratory distress syndrome, renal disease, trauma, multiple sclerosis, malaria, and liver injury. The strength of the correlation between the magnitude of decline in pGSN and likelihood of mortality is especially striking (see Publications). Its depletion in the blood precedes and predicts poor outcomes in humans. Even more compelling is the finding that repletion of pGSN improves survival in numerous animal models.

Key Takeaways

  • The strength of the correlation between the magnitude of decline in pGSN and likelihood of mortality is especially striking.
  • Its depletion in the blood precedes and predicts poor outcomes in humans.
  • Repletion of pGSN improves survival in numerous animal models.

Plasma Gelsolin Has Several Unusually Attractive Features. Plasma Gelsolin is a multifunctional protein whose multiple mechanisms of action improve disease outcomes. Replacement therapy is a well-accepted approach and restoring depleted levels of an endogenous human protein is likely to have few safety issues, compared to new chemical entities or antibodies in development……..

plasma gelsolin table

Plasma Gelsolin’s Biological Role: Protect and Defend

infographicPlasma gelsolin is a multi-functional protein. It improves disease outcomes by scavenging toxic actin which may be exposed in tissues or in plasma due to injury or infection. It also prevents the spread of inflammation from target sites by binding inflammatory mediators and enhances pathogen clearance via improved macrophage uptake and killing of gram-positive and gram-negative microorganisms.

This distinguishes plasma gelsolin from other anti-inflammatory agents which function as antagonists of individual mediators or inhibitors of specific enzymes and work to ablate inflammation. Most systemic anti-inflammatory agents also suppress the immune system and many require caution in administration because they increase the risk of infection. Plasma gelsolin is unique in that it enhances the antimicrobial action of macrophages, which engulf and digest cellular debris and pathogens, boosting immunity against both gram positive and gram negative bacterial infections.

Millions of years of evolution have designed plasma gelsolin to allow inflammation to continue locally, where it is needed, and at the same time boost the body’s immune response by impacting the ability of macrophages to kill pathogens. Plasma gelsolin’s ability to both fight infection and localize inflammation represents a major scientific breakthrough.