Mitochon Pipeline

Optic Neuritis (pre-MS)

• Inflammatory demyelinating disease of the optic nerve.
• Either idiophathic or associated with multiple sclerosis.
• Presentation: Acute unilateral vision loss.
Progresses 1-2 weeks.
Pain on eye movement.


• Significant retinal ganglion cell (RGC) axonal loss occurs following optic neuritis.
• Permanent vision loss from death of RGCs.
Pain on eye movement.

Optic Neuritis: Vision Loss

• Acute vision loss from inflammation and demyelination .
Improves when inflammation resolves.


• Permanent vision loss from death of RGCs.
No improvement after inflammation.

OUR DATA SHOWS:
MP201 prevents RGC loss during experimental optic neuritis.

• Reduces demyelination without suppressing inflammation.
• Preserves visual function. (Optokinetic Responses)

Known effects on mitochondria and oxidative stress suggest common mechanism of neuroprotection.

MP201 treatment attenuates RGC loss. Neuroprotective effects of MP201 were evaluated by counting RGCs immunolabelled with Brn3a antibody in 12 standardized fields, three from each quadrant of the retina. A. RGC loss in eyes of EAE mice (**p<0.01 vs control, N=10 eyes) is reduced by 16 mg/kg MP201 treatment from day 15 to 42 (p<0.001 vs EAE, N=10). 80 mg/kg MP201 also induces a significant (p<0.05 vs EAE, N=10) improvement in RGC numbers. B. Representative images show RGCs in one field of retina from each group (original magnification X20).

MP201 treatment significantly reduces axonal loss in optic neuritis. Neurofilament staining was used to evaluate axonal loss in sections of optic nerves isolated at day 42 post-immunization. A. The optical density of neurofilament staining calculated from three equal sized fields from each optic nerve shows a significant decrease (***p<0.001) in optic nerves (N=10 nerves) from EAE mice compared to optic nerves (N=10) from control mice. Treatment with 16 mg/kg (@@@p<0.001, N=10) or 80 mg/kg (@@p<0.01, N=10).

MP201 treatment attenuates demyelination in optic nerves during EAE. To examine whether MP201 treatment prevents demyelination, optic nerves were isolated from mice 42 days post-immunization, and were stained with LFB. A. LFB stained optic nerve longitudinal sections were examined by a blinded investigator and demyelination was quantified on a 0-3 point scale. optic nerves (N=10 nerves) from EAE mice had a significantly (**p<0.01) higher demyelination score compared to optic nerves (N=10) from control mice, and treatment with 16 mg/kg (@@p<0.01 vs EAE, N=10) or 80 mg/kg (@p<0.05 vs EAE, N=10) MP201 lead to a significant decrease in demyelination scores. B. A representative image of one optic nerve from a PBS-treated EAE mouse shows less LFB (blue) staining than an optic nerve from a control mouse, as well as optic nerves of EAE mice treated with either 16 mg/kg or 80 mg/kg MP201 (original magnification X20.