oSLO (“o” for oxidized, “SLO” for StreptoLysin O) is derived from Streptolysin O (SLO), a biologic from Group A beta-hemolytic streptococci which is spontaneously oxidized when placed in water, thereby becoming oSLO. In the doses used to treat animals, oSLO is much less toxic than a therapeutic dose of aspirin, and it is expected to demonstrate the same margin of safety in formal FDA animal trials which are currently underway and in similar human trials planned for the next year.
Mechanism of Action
Evidence from multiple sources suggests that low doses of oSLO can reduce adverse aspects of the inflammatory response and improve its beneficial ones, thereby reversing the chronic effects of TBI. The reduction of inflammation in the damaged brain decreases swelling, stimulates healing, decreases further long-term insult in the afflicted area, and may reduce neurodegeneration. This hypothesis is supported by both genomic analysis and animal experiments.
To determine the impact of oSLO on the inflammatory response, an independent laboratory completed an mRNA analysis of the expression of over seven hundred genes covering more than twenty biochemical pathways in a highly active class of inflammatory cells (dendritic cells) that were exposed to multiple doses of oSLO. Their data showed downregulation of injurious cytokine signaling and upregulation of the beneficial integrated stress response.
“…the mechanism … is to quell the neuroinflammatory phase of TBI through the reprograming of dendritic cells, the sentinel antigen presenting cells, which can in turn modulate the neuro inflammatory response throughout the brain and the entire body.”
Management and the Company’s Scientific Advisory Board have been unable to identify any animal models which have been proven to accurately predict outcomes in chronic TBI. The company has conducted experiments in animals with short term, acute TBI where serial, controlled blows to the head create a brain injury. In one instance, a third party performed a set of experiments which demonstrated how oSLO helped restore memory in concussed mice to approximately the same level as non-concussed mice at the end of a multi-day treatment and testing period. In contrast, concussed mice treated with a placebo had memories that remained impaired.
When the mice were sacrificed at the end of the experiment, inflammatory cells in oSLO-treated concussed mice had been reduced from initial levels to levels that were equivalent to non- concussed mice and less than concussed animals who received no treatment.
These experiments in acute TBI support the genomic observations above because oSLO inhibited the cells which induce inflammation.