Tuesday, 9 July 2013

Throwing the bady out with the bathwater


Fiebiger SM, Bros H, Grobosch T, Janssen A, Chanvillard C, Paul F, Dörr J, Millward JM, Infante-Duarte C.The antioxidant idebenone fails to prevent or attenuate chronic experimental autoimmune encephalomyelitis in the mouse. J Neuroimmunol. 2013 doi:pii: S0165-5728(13)00174-4.
Oxidative stress and mitochondrial dysfunction appear to contribute to neurodegenerative processes during multiple sclerosis (MS). Thus, antioxidants may represent a therapeutic option for MS. The antioxidant idebenone was proven to be beneficial in Friedreich's ataxia and Leber's hereditary optic neuropathy, two disorders caused by mitochondrial alterations. Here we showed that idebenone protected neuronal HT22 cells from glutamate-induced death in vitro. However, in experimental autoimmune encephalomyelitis, idebenone failed to affect disease incidence or onset when applied preventively, or to reduce disease severity when applied therapeutically. Histopathological examination of CNS from idebenone treated mice showed no improvement in inflammation, demyelination, or axonal damage. Thus, we hypothesize that idebenone treatment will likely not benefit patients with MS.

                  Does it possitively affect brain chemistry?
 
The message from this study is load and clear idebenone is rubbish.
 
It was hoped that it could target progressive neurodegeneration, so it was tested in EAE and it failed to do anything and did not alter disease incidence or onset. So authors are dispondent and drug gets cast asside. 
 
However the EAE immunology dogma has clouded the issue. A pure neuroprotective drug should not affect this and this is what you get.  click here
 
However it apparently did not affect nerve loss which would be hoped, 
 
However without the right models and interpretation we may throw away useful molecules

1 comment:

  1. New to this, but agree with you - don't think this mouse study has any forecasting ability on idebenone's future capabilities in PPMS. Looking at a similar paper that characterized EAE chronic vs. Relapsing, and comparing it to the idebenone paper, it looks like the mice are exhibiting the relapsing form of disease, not the chronic/progressive. See figure 1, below and compare to Figure 3 in the idebenone paper.

    http://onlinelibrary.wiley.com/doi/10.1002/glia.20935/full

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