Friday, 13 November 2015

Sulfasalazine and remyelination

Kim S, Lee YI, Chang KY, Lee DW, Cho SC, Ha YW, Na JE, Rhyu IJ, Park SC, Park HC. Promotion of Remyelination by Sulfasalazine in a Transgenic Zebrafish Model of Demyelination. Mol Cells. 2015. doi: 10.14348/molcells.2015.0246. [Epub ahead of print]
Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immunomodulating drug that is used in rheumatology and inflammatory bowel disease. 

Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

So what will happen will it be looked at in EAE it made things better or worse and in MS the data  was not that impressive

Correale J, Olsson T, Björk J, Smedegård G, Höjeberg B, Link H. Sulfasalazine aggravates experimental autoimmune encephalomyelitis and causes an increase in the number of autoreactive T cells. J Neuroimmunol. 1991;34:109-20.

Failure of sulfasalazine to influence experimental autoimmune encephalomyelitis.Uitdehaag BM, Polman CH, de Groot CJ, Huitinga I, Dijkstra CD.Acta Neurol Scand. 1991 ;84(2):173-4.
Suppression of experimental autoimmune encephalomyelitis by sulfasalazine.Prosiegel M, Neu I, Vogl S, Hoffmann G, Wildfeuer A, Ruhenstroth-Bauer G.Acta Neurol Scand. 1990;81(3):237-8.
Suppression of experimental autoimmune encephalitis by sulfasalazine.Prosiegel M, Neu I, Ruhenstroth-Bauer G, Hoffmann G, Vogl S, Mehlber L, Wildfeuer A.N Engl J Med. 1989 Aug 24;321:545-6.

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.Noseworthy JH, O'Brien P, Erickson BJ, Lee D, Sneve D, Ebers GC, Rice GP, Auty A, Hader WJ, Kirk A, Duquette P, Carter J, Francis G, Metz L, Shuster E. Neurology. 1998; 51(5):1342-52.Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, these positive findings were not sustained into the second half of the trial.

2 comments:

  1. Is it because most substances used in rheumatoid arthritis inhibit TNF alpha activity and this is proven EAE / MS worse ?!

    ReplyDelete

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