Lactoferrin

Lactoferrin is an iron-binding antimicrobial protein (~80kD) found in various mammalian secretions, including milk, and within the secondary granules of neutrophils. It is highly stable and protease resistant, with a pI > 9.0 and a high degree of disulfide bonds. The protein is bilobal and can bind two iron molecules. Its good safety profile and multifunctional benefits make it a valuable human therapeutic.

Source of Lactoferrin

Production of recombinant human lactoferrin utilizes yeast fermentation to produce large volumes of the protein. Yeast is a well established, cost effective production technology that also scales well. Specific expression systems are used for the production of lactoferrin with appropriate glycosylation (sugars that are attached to the protein). This fully humanized recombinant lactoferrin has the advantage of being able to be used intravenously. There are no other companies able to sell recombinant normal human lactoferrin.

Bovine lactoferrin, although available commercially (byproduct of cheese production), can only be used orally, and cannot be injected intravenously. This is due to insufficient homology between bovine and human molecules that may cause severe antigenic reaction, including anaphylactic shock.

 

 

Prevention of SIRS Progressing to Sepsis

SIRS, systemic inflammatory response syndrome, is a common problem with 68% of ICU patients presenting. There are no specific current treatments to prevent SIRS from progressing to sepsis. Fluid management and antibiotics are administered, but the deleterious immunological cascade may have already progressed too far and too fast. There is currently one FDA approved drug specifically for treating severe sepsis. Trials in children were stopped for lack of efficacy and the serious side effect of stroke has precluded its use in earlier stages of sepsis. The current price of over $6,000 has also prevented widespread utilization.

SIRS and sepsis are but two examples of oxidative stress-related disorders that can be treated with lactoferrin.

Clinical Trials

A phase I clinical trial in Trauma ICU Patients is planned. A clinical trial site has been selected and clinical protocols are being developed. Exclusion criteria have been developed. Clinical endpoints will include prevention of multiple organ failure and death.

  
 

Basic Mechanism

Lactoferrin provides multiple clinical effects, the most important seen to the right. The immune modulation is important in quelling an overheated immune response, so that the patient does not go into shock and organ failure. Immune modulation includes down-regulating damaging cytokine production and immune augmentation through enhancing the differentiation of immune system cells.

The combination of immune modulation and
  antimicrobial activity are believed to play an
   important role in preserving the integrity of the gut,
  thus preventing further infection from the invasion
of microbes leaking from the gut into the circulation..