Saturday, 3 September 2016

Tamoxifen induces remyelination


Gonzalez GA, Hofer MP, Syed YA, Amaral AI, Rundle J, Rahman S, Zhao C, Kotter MR. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system.
Sci Rep. 2016;6:31599.

Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of Protein Kinase Cα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition,

Another protein kinase C which is serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. Protein kinase C-alpha (PKC-α) is a specific member of the protein kinase family. These enzymes are characterized by their ability to add a phosphate group to other proteins, thus changing their function. This molecule is involved in the development of oligodendrocytes.


 In studying ways to stop blockade of differentiation to oligodendrocytes they found that tamoxifien which blocks oestrogen receptors, could promote remyelination.

One suspects that a number of females with MS, have recieved tamoxifen as part of breast cancer therapy. Has this improved their MS

3 comments:

  1. My sister was offered Tamoxifen after having a cancerous breast removed at the beginning of the year. She turned it down, in part because it brings on immediate menopause. I thought women with MS generally do worse after the menopause because oestrogen is neuro-protective. What's MD's view on this?

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    Replies
    1. My partner was on tamoxifen for 5 years, and was diagnosed with MS 2 or 3 years after finishing tamoxifen lol.

      Cordelia, from memory tamoxifen can cause but it doesn't have to cause menopause on its own. alongside tamoxifen, my partner was treated for cancer with estrogen depleting injections (ie. she was put into induced menopause for 5 years, independently from the effects of tamoxifen.

      we had always wondered whether 5 years of induced menopause kicked the ms into overdrive.

      now i know that if my partner was a mouse, then even if induced menopause kicked the ms into overdrive, the tamoxifen would have kept her nerves more remyelinated more than otherwise.

      Wonder what all that's worth lol.

      Wonder what will happen with her MS in the future lol.

      Wonder what the next affliction that befalls her will be (call me a pessimist, but I have no hope left that MS will be the end of it lol).

      Funny life.

      Delete
  2. So my doubts "eternal" in relation to sex hormones.
    If tamoxifen helps remyelinate by just block estrogen, contraceptives would have the reverse action, because of constant delivery of estrogen?

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