In a number of human diseases, chronic activation of the innate immune system cells, macrophages and microglia, exacerbates the release of pro-inflammatory cytokines and chemokines, creates an environment of hyperinflammation and tissue damage and neuroinflammation and neuronal loss in the brain. If left unchecked, this can lead to significant morbidity and mortality.
In multiple pre-clinical models, OP-101, has been show to shut down all pro-inflammatory cytokines expressed by reactive macrophages and microglia and return them to a healthy phenotype. We have begun dosing severe COVID-19 patients in a phase 2 study designed to examine the effects of OP-101 in shutting down all pathways of cytokine production and excessive inflammation. We believe that addressing the inflammatory production at the cellular level (macrophages and microglia) could have a more robust effect than therapeutics targeting cytokine reduction individually.
Mechanism of Action
- OP-101 (HD-n-acetyl cysteine) is selectively taken up by reactive macrophages
- Mechanism demonstrated in animal models of LPS induced inflammation (ARDS, TB, neuroinflammation, etc)
- After uptake, OP-101 returns macrophage to “normal” shutting down IƘƘβ and NFƘβ pathways and inhibits JAK/STAT/MAPK
- OP-101 also reduces oxidative stress (corticosteroids do not address oxidative
Neuroinflammation and Neurogenerative Diseases
- We have established in multiple models of neurodegeneration that HD therapeutics cross the blood brain barrier (BBB) and are selectively taken up by reactive microglia at the site of inflammation and pathology
- HD-Cy5 is taken up by plaque associated microglia and may offer up novel solutions to target reactive microglia in Alzheimer’s patients and other neurodegenerative conditions.
- To explore this further, we are developing OP-801, a radiolabeled (18F) HD, as a companion diagnostic to enable patient to enable patient selection followed by treatment with anti-neuroinflammatory agent coupled to HD to target reactive microglia