Friday, 17 April 2015

On the way to treating progressive MS

Last week we had a lot of interest in Biotin Day.

Some of you have taken matters into your own hands.

Only a week to go before for we find out what's in the Plenary session at the AAN....will Biotin day be a day to remember or forget?
      

However the press release today  states that the trial was a success. So good news for MSers

But whilst on cheap as chips treatment this is not MS. But this is something interesting that cropped up in the News. 

Kan MJ et al. Arginine Deprivation and Immune suppression in a mouse model of Alzheimers Disease J Neurosci 35:5969-5982
The pathogenesis of Alzheimer’s disease (AD) is a critical unsolved question; and although recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction and death is unknown. We have previously described the unique CVN-AD mouse model of AD, in which immune-mediated nitric oxide is lowered to mimic human levels, resulting in a mouse model that demonstrates the cardinal features of AD, including amyloid deposition, hyperphosphorylated and aggregated tau, behavioural changes, and age-dependent hippocampal neuronal loss. Using this mouse model, we studied longitudinal changes in brain immunity in relation to neuronal loss and, contrary to the predominant view that AD pathology is driven by proinflammatory factors, we find that the pathology in CVN-AD mice is driven by local immune suppression. Areas of hippocampal neuronal death are associated with the presence of immunosuppressive CD11c microglia and extracellular arginase, resulting in arginine catabolism and reduced levels of total brain arginine. Pharmacologic disruption of the arginine utilization pathway
by an inhibitor of arginase and ornithine decarboxylase protected the mice from AD-like pathology and significantly decreased CD11c expression. Our findings strongly implicate local immune-mediated amino acid catabolism as a novel and potentially critical mechanism mediating the age-dependent and regional loss of neurons in humans with AD. 

In MS there is talk of a  change in balance between good and bad microglia the immunosuppressive microglia are thought to be those that induce remyelination. Many moons ago I looked at EAE lesions to see what type of macrophages were present and they were stuffed full of CD11c positive cells=, which clearly were not dendritic cells which also express CD11c. So the question is posed could a simple chemical like ornithine decarboxylase make the difference. As ever this is basic research and it has to translate to see if it works in Alzheimers disease and likewise there is no evidence that this approach will be of use in MS...so please,please do not try this at home.

MD2 is chomping at the bit.

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