Tuesday, 27 March 2012

Research: Remyelination and Galanin.. another way

Zhang et al. Galanin Transgenic Mice with Elevated Circulating Galanin Levels Alleviate Demyelination in a Cuprizone-Induced MS Mouse Model.PLoS One. 2012;7(3):e33901. Epub 2012 Mar 19.

MS is a demyelinating autoimmune disease of the central nervous system (CNS) with a presumed autoimmune etiology. Approved treatments for MS are immunoregulatory and are able to reduce the inflammatory components of the disease. However, these treatments do not suppress progressive clinical disability. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination are likely to improve long-term outcomes and reduce the rate of axonal damage. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system and has diverse neuromodulatory effects. In this study, using the cuprizone (CPZ) demyelination model of MS, we demonstrate that GAL has pronounced neuroprotective effects with respect to demyelination and remyelination. Using our GAL transgenic mouse (GAL-Tg), we identified a novel attenuation of OLs against CPZ induced demyelination, which was exerted independently of progenitor cells. Alleviation of myelin breakdown in the GAL-Tg mice was observed to be significant. Furthermore, we observed changes in the expression of the GAL receptor GalR1 during the demyelination and remyelination processes. Our data strongly indicate that GAL has the capacity to influence the outcome of primary insults that directly target OLs, as opposed to cases where immune activation is the primary pathogenic event. Taken together, these results suggest that GAL is a promising next-generation target for the treatment of MS.

Cuprizone is a toxin to certain oligodendrocytes in mice. This is yet another target for promoting repair. We had had a load of these new avenues, yet none have bourne fruit so far. This is encouraging as we have another way to modify this process.


  1. I've re-read your blogs on progression using the analogies of green cars/carpark/tube system. Presumably if you hit early stage MS aggressively with something like alemtuzumab, especially in a young person, then the likliehood of progression being the result of the car park floor collapsing is minimal (you need to see the analogy, for those who haven't). Therefore, progression would be due to problems with the tube system (nerve network) itself in that a blockage on a line(axon) leads to tube trains(impulses)using a different line that gets over crowded and fails, leading to another blockage and thus progression. However, I thought the brain had loads of spare capacity unlike the spinal cord.

    Also where does BG12 fit into this. Is it an immunomodulator? I read it was neuroprotective and anti-inflammatory, thus dealt with inflammation, the product of the immune system, rather than with the immune system itself.

  2. There is spare capacity but eventually that gets used up.
    BG12 inhibits relapse in RRMS presumably by inhibiting the immune response or having anti inflammatory action. It has potential to do more but this has yet to be shown.


Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.