Huntington’s Disease: proof of concept
- Noninvasive IV injection of nanoparticles of the OCCT complexed electrostatically to an ASO (OCCT:ASO)
- Very low effective dose (1/100th of the dose used intrathecally by competitors)
- No signs of toxicity during in vivo rodent studies up to 6 months
- Halts the progression of Huntington's disease and reduces HD protein in the most severe humanized mouse model (Figure 1)
- Reduces Huntingtin protein expression in different brain regions in mice and monkeys up to 57% (Figure 2)
- Increases brain uptake up to 6.4x in monkeys (Figure 2)
Figure 1. Halts the progression of Huntington's disease and reduces HD protein level. Restores normal rearing activity and decrease of HD protein correlating with behavior improvement in zQ175 humanized Huntington’s disease mouse model with 0.1 mpk dose of Ophidion’s lead OCCT:ASO. The OCCT:ASO was administered IV bimonthly forfor 3 months.
Figure 2. Reduces Huntingtin protein (HTT) expression in different brain regions and increases brain uptake in NHPs. Significant reduction of soluble wild-type HTT protein in various brain tissues hippocampus, striatum, motor cortex, and somatosensory cortex) in NHP injected with 0.3 mpk dose of OCCT:ASO. The TOCCT:ASO was administered IV bimonthly for 3 months for the protein reduction study and 1.5 months for the brain uptake study.