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oSLO

oSLO Platform

OSLO SELECTIVELY RESTORES THE HEALTHY CENTRAL NERVOUS SYSTEM MICROENVIRONMENT

Streptolysin O is a Cholesterol Dependent Cytolysin (CDC) and an exotoxin of group a B-hemolytic streptococcus bacteria.  It has an elongated structure composed of four different domains which can create pore complexes within the cell membrane and cause hemolysis1

The oxidized form of Streptolysin O (oSLO) is non-toxic and can no longer bind with the cholesterol and form pores. It is 1/10,000th of the lethal dose concentration of reduced streptolysin.
 
oSLO is a biologic comprised of a low concentration of oxidized streptolysin O molecules diluted in phosphate-buffered saline. 
 
Oxidized concentrations can affect host immune signaling 2-4

oSLO Regulates Gene Expression in Mature Human Dendritic Cells

WITHIN 48 HOURS OF EXPOSURE TO DRUG, STATISTICALLY SIGNIFICANT CAHNGES IN GENE EXPRESSION OCCUR

Background & Rationale

  • Dendritic Cells (DC) are the pre-eminent sentinel antigen-presenting cells of the immune system1

  • In TBI mouse model, DCs can change their subtype in the brain and throughout the circulatory and lymphatic systems after a TBI event2

  • TBI at both early and late stages alters DC differentiation concomitant with a reduction of reactive oxygen species levels (ROS) in neuroprogenitor cells.

  • DCs may regulate the chronic manifestations of TBI because they act on many other cell types.

Method

  • Human mature dendritic cells harvested and treated with purified oSLO.

  • Cells harvested and RNA isolated – RNA concentration was determined &  normalized to 20µg/mL.

  • Gene microarray analysis using NanoString nCounter® Human Neuroinflammatory panel

    • 770 Genes & 23 Pathways

 

Results

  • Biochemical pathways involved include: Cytokine signaling, Integrated Stress Response, Autophagy & Growth factor signaling

  • Cognitive genes downregulated:

    • PLA2G4A – associated with delirium, dementia, amnesia and cognitive disorders

    • CD209 – associated with psychogenic disorders

oSLO Gene Expression

Multiple mechanisms of action

OSLO SHOWN TO IMPACT MULTIPLE PATHWAYS TOWARD HEALING

Keratinocytes

Wound Healing

Keratinocytes

10 genes upregulated
(p< 0.031)

Macrophages

Modulate Immune Response

Macrophages

1 gene downregulated
3 upregulated

(p<0.037)

Neural Progenitor Cells

Brain Repair & Regeneration

Progenitor Cells

8 genes upregulated
(p<0.040)

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