OUR SCIENCE
Iron Binding Polymers
From our deep understanding of iron acquisition by microbial pathogens and cancer cells and how our bodies regulate iron metabolism and also attempt to withdraw iron during disease, we have developed a new platform of advanced iron binding polymer compounds. DIBI (Denying Iron to Bacterial Infections), a current lead, is a purpose-built co-polymer of two different subunits, one of which binds iron. There are 9 iron-binding subunits per polymer enabling each molecule of DIBI to bind three iron molecules completely. DIBI binds iron 1,000 times more strongly than the currently used medical chelators and in a highly stable non-reactive safe form. This DIBI bound iron is not available to pathogens and therefore DIBI exploits the absolute requirement of pathogens for iron to grow and reproduce, by binding the iron they use, making it inaccessible, augmenting a natural iron sequestration mechanism, the hypoferremic response, to starve infections.
This water-soluble polymer is ideal for many different routes of administration and has been characterized in 22 published studies so far, showing a broad spectrum of antimicrobial activity against bacterial and fungal infections, including drug resistant organisms. It is non-toxic to normal uninfected cells, and because of its unique mechanism of action, it is immune to the development of microbial resistance – pathogens can’t become resistant to needing iron. DIBI is also effective against sepsis and inflammatory disorders, downregulating the cytokines implicated in cytokine storm in sepsis.
In animal models, DIBI has been delivered orally, topically (to the skin), intravenously (IV), intraperitoneally (IP), to the ear, eye, nose, and vagina (for vaginitis).
In animal models, DIBI has been delivered:
Orally
Topically
(to the skin)
Intravenously
(IV)
Intraperitoneally
(IP)
To the ear, eye, nose
Cancer cells exposed to DIBI show a strong hypoferremic response
Cancer cells exposed to DIBI show a strong hypoferremic response; as DIBI is increased in concentration, iron storage goes up, iron export from cells is shut off and iron import is increased.
Initial disease targets include those where an abundance of bioavailable iron, due to saturation or dysregulation of normal iron management, exacerbates the disease. Foremost among these are infectious diseases.
The three small molecule chelators approved by the FDA are not viable alternatives to DIBI. When re-purposed for infectious disease in animal models, these small molecule chelators showed poor results. They mobilize intracellular host iron, in some cases making iron more available to pathogens. Combined with their toxicities, this makes them inappropriate for anti-infective use.
