All About Plasma Gelsolin – Answers to Common Questions

BioAegis is developing a therapeutic based on the human protein plasma gelsolin for the treatment of inflammatory, infectious and degenerative diseases.

Plasma gelsolin (pGSN) is a naturally occurring, abundant human protein that is an important part of the innate immune system which provides the first line of defense against threats. It has an ancient origin early in evolution.

Plasma gelsolin is a master regulator of immune function.  Its mechanism of action is complex and multi-pronged:

  1. Initially, pGSN travels to the site of injury and assists tissue macrophages by binding to and clearing cell debris released from dead cells, including actin and DNA, increasing the macrophage’s ability to attack pathogens.
  2. pGSN boosts the immune function of macrophages to have greater uptake and killing of pathogens.
  3. The systemic supply of pGSN prevents the spread of inflammation to key organs by binding to and clearing inflammatory mediators, keeping the inflammatory response local to the site of injury.
  4. pGSN enables a signaling system (quorum sensing) in macrophages that regulates the transition of these cells from a pro-inflammatory state into an anti-inflammatory state.
  5. Importantly, pGSN is not immunosuppressive like other anti-inflammatory agents.

Gelsolin was discovered in the Harvard lab of Thomas P. Stossel, a professor of medicine and American physician-researcher. He and his colleagues and collaborators identified the unique role of plasma gelsolin to address injury and infection. BioAegis was formed to license this intellectual property and pursue its commercialization.  Since its formation, BioAegis has extended the knowledge of plasma gelsolin through collaboration and internal research and advanced its clinical development into Phase 2.

The body’s supply of plasma gelsolin becomes depleted when faced with a threat – inflammation, infection, trauma, etc. Binding to cell debris and sequestering inflammatory mediators consumes the available supply, putting the patient at risk.  The more severe the disease, the greater the depletion of gelsolin and the higher the risk of poor outcomes.  By administering BioAegis’ recombinant form of pGSN, the levels can be restored and pGSN can continue to protect and defend.

A host-directed therapeutic (HDT) is one that can work to amplify the body’s own natural responses.  In this case, it impacts the body’s own protective immune responses to reduce excessive inflammation and to optimize immune reactivity at the sites of disease. In the case of infection, this contrasts with therapeutics that target and treat specific pathogen threats while the host-directed therapeutics are able to address multiple threats by empowering our own system. They are  “pathogen-agnostic,” meaning that they work on multiple threats, including drug resistant and new or mutated pathogens.

HDTs are particularly important in the areas of infection and inflammation because:

  • In many cases of severe infection, by the time a patient’s life is threatened, the immune system has already dealt with the virus or bacteria.  Mortality is a direct result of an out of control inflammatory response that can damage the otherwise healthy organs.
  • HDTs are pathogen-agnostic which means they can be effective regardless of the emergence of new pathogens or new strains, because they target the host/body’s immune response, not the bacterium or virus. This is important for future pandemics.

Steroids are very good at reducing inflammation but at the cost of decreasing the immune system’s ability to fight infection. They are known to be immunosuppressive and are a risky treatment option for compromised patients or for long term use. While they have been effective in treating severe COVID-19, they are not effective in many other infectious diseases.  Plasma gelsolin is unique in that it is able to control excess inflammation while at the same time boosting the immune system’s infection fighting effort. Plasma gelsolin is not immunosuppressive.

Rhu-pGSN is not currently available for human use but is currently being used in human clinical trials and animal research.  BioAegis supplies academic collaborators around the world with recombinant gelsolin to extend our understanding of its important role in the immune system. BioAegis protects its commercial rights with its patent portfolio and continues to innovate and file new intellectual property. BioAegis has considerable know-how, including that pertaining to the production of plasma gelsolin under GMP (Good Manufacturing Practices) that allows us to use it in clinical trials.

Recombinant means that the protein is manufactured using technology which inserts the genetic code for a protein into a cell to produce a copy of that protein without the use of any animal materials.  This product is then purified to produce high quality material for research, clinical or commercial use, based on defined regulatory standards.  This is how we produce recombinant human plasma gelsolin (rhu-pGSN).

Several companies are selling Enzyme-Linked Immunosorbent Assay (ELISA) testing kits to measure plasma gelsolin for research purposes only. BioAegis has a proprietary ELISA testing method which has been validated for use in clinical trials and has developed key analytical methods important for manufacturing and clinical development. 

BioAegis has built a strong patent estate and continues to actively expand its patent coverage.  More than 42 patents have been issued, with many more under review worldwide. We have filed new patent applications during 2019, 2020 and 2021, which are in various stages of the prosecution process, covering a wide range of applications.