Lactillion, Inc.

	Focus Lactoferrin is a multifunctional protein with many commercially valuable applications, particularly in what are called oxidative stress-related disorders. Lactillion's product focus on preventing and treating sepsis is based on many years of significant research performed by Dr. Marian Kruzel and many collaborating scientists. Production of recombinant human lactoferrin opens the door to many clinical indications that require systemic delivery via intravenous injection.
	Mechanism of Action Lactoferrin's pleiotropic actions converge to help retain the integrity of the gut. As shown in the histology panels below, the intestinal lumen becomes disrupted and can leak the contents of the intestine into the circulation when mice are treated with LPS (lipopolysaccharide) to induce endotoxemia. LPS is particularly immunostimulatory; when given at high enough concentrations it will kill the animal. In mouse models where 100% of the LPS-treated mice die, administration of lactoferrin orally saves 50-80% of the mice and intravenous administration saves 100% of the mice. In addition to preventing intestinal bacteria from overwhelming the mice, lactoferrin is able to mute the hyperinflammatory immune response to LPS.
	Role of the N-Terminus The left end of the lactoferrin protein contains amino acids that have important binding sites for heparin, LPS, and bacteria. Mutations in amino acids 11 and 29 have been correlated with human pathology (increased rate of periodontitis) by Dr. Daniel Fine and colleagues at UMDNJ. Lactillion is the only company able to produce normal human lactoferrin that does not have these mutations.	Glycoforms There are three primary sites of N-glycosylation on the lactoferrin protein as shown below. From research done by Dr. Kruzel and others, it is apparent that glycosylation is important in lactoferrin binding. Lactillion is developing glycoforms of lactoferrin to optimize the protein's bioactivity.
	Lactoferrin and Iron-Dependent Oxidative Stress By virtue of iron sequestration, lactoferrin can control the physiological balance between reactive oxygen species (ROS) production and the rate of their elimination, which naturally protects against the oxidative cell injury. Oxidative stress has been implicated in a variety of pathological and chronic degenerative processes including the development of cancer, atherosclerosis, inflammation, aging, neurodegenerative disorders, and defense against infection. Under normal physiological conditions, the rate and magnitude of reactive oxidant formation is dependent on the availability of the transition metals. In particular, traces of iron can be detrimental to physiological processes under reactive oxygen conditions. Indeed, iron is in the center of the reactive oxygen species control, so is lactoferrin too. Our research focus on understanding the mechanism of action of LF, which links many signaling pathways, responsible for either cessation or progression of pathological events in our body.
	New Clinical Indications Lactillion is committed to utilization of lactoferrin both directly and through licensing to third parties. There are many potential additional clinical uses. Current projects include lactoferrin for use in Vaccines Burn therapies Anti-aging medicine Allergy Partnerships are also being developed in the area of genetic screening for deleterious polymorphisms.