Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis
The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are pr...
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Online Access: | http://dx.doi.org/10.1155/2017/7180632 |
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doaj-fc189ea9af0e4b5587e7bc71804045002020-11-24T22:14:47ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942017-01-01201710.1155/2017/71806327180632Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic NeuritisReas S. Khan0Kimberly Dine1John G. Geisler2Kenneth S. Shindler3Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USAScheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USAMitochon Pharmaceuticals, Inc., 970 Cross Lane, Blue Bell, PA, USAScheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USAThe ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria’s physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis.http://dx.doi.org/10.1155/2017/7180632 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Reas S. Khan Kimberly Dine John G. Geisler Kenneth S. Shindler |
spellingShingle |
Reas S. Khan Kimberly Dine John G. Geisler Kenneth S. Shindler Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis Oxidative Medicine and Cellular Longevity |
author_facet |
Reas S. Khan Kimberly Dine John G. Geisler Kenneth S. Shindler |
author_sort |
Reas S. Khan |
title |
Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis |
title_short |
Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis |
title_full |
Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis |
title_fullStr |
Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis |
title_full_unstemmed |
Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis |
title_sort |
mitochondrial uncoupler prodrug of 2,4-dinitrophenol, mp201, prevents neuronal damage and preserves vision in experimental optic neuritis |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2017-01-01 |
description |
The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria’s physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis. |
url |
http://dx.doi.org/10.1155/2017/7180632 |
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