Study Rationale:
Inflammation of the central nervous system mediated by microglial cells is a major feature of Parkinson’s disease. Vivreon Biosciences is developing Parkinson’s disease therapeutics that target microglia CRAC channels, a calcium channel that has been shown to be required for initiating neurotoxic processes and that has been detected at high levels in the brains of healthy individuals. Here, we intend to prove that it is also is present in Parkinson’s disease brains and that Vivreon compounds selectively inhibit the CRAC channel, suppressing neurotoxicity.
Hypothesis:
Vivreon hypothesizes that CRAC channels are present at detectable levels in Parkinson’s disease brains and that Vivreon compounds suppress microglial-derived neurotoxic genes through selective inhibition of CRAC channels.
Study Design:
Fixed brain tissue from control and Parkinson’s disease individuals will be assessed for CRAC channel levels to show that CRAC is present in Parkinson’s disease individuals. Microglia cells will be stimulated with alpha-synuclein and treated with Vivreon compounds and analyzed for genome-wide transcription levels, focusing on neurotoxic inflammatory genes to show that Vivreon’s CRAC channel inhibitors suppress these processes in a Parkinson’s disease-like model. Vivreon’s CRAC channel inhibitors will also be screened against 44 different ion channels, enzymes and receptors to show that their effects are due to selective CRAC channel inhibition.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This research will identify an entirely new target for Parkinson’s disease intervention, the CRAC channel, and will help to further characterize a first-in-class novel therapy that blocks this target.
Next Steps for Development:
Following completion of these studies, Vivreon will work to improve properties like potency, brain distribution and safety of their most promising compounds before selecting one to move into human trials for therapeutic drug candidacy.