Thursday, 8 June 2017

Anti-Depressent Painkiller could influence myelination

Chami M, Halmer R, Schnoeder L, Anne Becker K, Meier C, Fassbender K, Gulbins E, Walter S. Acid sphingomyelinase deficiency enhances myelin repair after acute and chronic demyelination. PLoS One. 2017; 12(6):e0178622.

The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair. Sphingolipids, in particular ceramide and the enzyme acid sphingomyelinase, which generates ceramide from sphingomyelin, seem to be involved in astrocyte activation and neuronal damage in multiple sclerosis. 

We used immunohistochemistry to study glial reaction and oligodendrocyte distribution in acid sphingomyelinase-deficient mice and wild-type C57BL/6 littermates at various time intervals after demyelination and remyelination. Axonal injury was quantified using amyloid precursor protein and synaptophysin, and gene expression and protein levels were measured using gene analysis and Western blotting, respectively. Our results show that mice lacking acid sphingomyelinase had a significant increase in myelin recovery and a significantly higher oligodendrocyte cell count after 2 weeks remyelination compared to wild-type littermates. Detrimental astroglial distribution was also significantly reduced in acid sphingomyelinase deficient animals. We obtained similar results in experiments using amitriptyline to inhibit acid sphingomyelinase. These findings suggest that acid sphingomyelinase plays a significant role in myelin repair, and its inhibition by amitriptyline may constitute a novel therapeutic approach for multiple sclerosis patients.

The main suggestion of this study is is that amitriptyline. This is a tricyclic (three cyclic chemical groups) anti-depressant. Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter however it has other targets. in this study it is reported to block sphingocine-myelinase. This is reported to promote myelination in  a model of demyelination. This clearly interesting, but first it has to be said this is an animal study not humans and there is no human evidence that it works for this activity. Next amitriptyline can influence how other drugs work and should not be added to your treatment without medical advice and next we need to see if the animal studies translate to human benefit as the doses used we about 10-20 times the human dose. So we will see.

5 comments:

  1. Some pwMS take amitriptyline for neopathic pain.

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    1. yes i know, but is there evidence for a recovery of symptoms, i am not a ware of this so it says be warned about expectations, the experiments where there is chronic demyelination with gliotic astrocytes is never done, one may guess the response may be very different. In the cuprizone model, do nothing and remyelination occurs it just happens abit quicker with the treatments.

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    2. In the same vain I found a bunch of pwMS who take oxcarbazepine for peripheral neuropathic pain and they don't seem to have a modified disease course. But anecdote is not study and these compounds probably have to be used over the course of decades to have a significant compound effect.

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  2. Of interest MD: https://www.sciencedaily.com/releases/2017/06/170606135744.htm

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  3. I read elsewwhere that muscarinic receptors play a role in myelination
    and amytriptilinie is a weak anticholinergic

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