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Reducing the side effects of a multiple sclerosis drug

Date:
May 9, 2011
Source:
Journal of Clinical Investigation
Summary:
The drug FTY720 is approved for the treatment of multiple sclerosis. Although highly effective it can have serious side effects. Understanding the molecular mechanisms by which the drug affects its target could lead to the development of a drug with the same therapeutic efficacy but reduced side effects. In this context, researchers have now detailed the molecular mechanism by which FTY270 causes adverse effects in the lungs of mice.
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The drug FTY720 is approved for the treatment of multiple sclerosis. Although highly effective it can have serious side effects, including reduced lung function and fluid accumulation in the eye. Understanding the multiple molecular mechanisms by which the drug affects its target (the S1P receptor) could lead to the development of a drug with the same therapeutic efficacy but reduced side effects.

In this context, a team of researchers, led by Timothy Hla, at Weill Cornell Medical College, New York, has now detailed the molecular mechanism by which FTY270 causes adverse effects in the lungs of mice.

Specifically, Hla and colleagues outlined a mechanism by which FTY270 causes S1P receptor degradation on the cells lining the blood vessels of the lungs and found that this reduction in S1P receptor levels causes leakage of the blood vessel contents into the lungs, impairing lung function.

In contrast, S1P receptor degradation appears not to be required for the effects of FTY720 on immune cells, which are the effects that mediate its therapeutic efficacy. Hla and colleagues therefore suggest that developing a drug that does not act on S1P receptor on the cells lining the blood vessels of the lungs but does target S1P receptor on immune cells may provide a therapeutic with decreased side effects.


Story Source:

The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Myat Lin Oo, Sung-Hee Chang, Shobha Thangada, Ming-Tao Wu, Karim Rezaul, Victoria Blaho, Sun-Il Hwang, David K. Han, Timothy Hla. Engagement of S1P1-degradative mechanisms leads to vascular leak in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI45403

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Journal of Clinical Investigation. "Reducing the side effects of a multiple sclerosis drug." ScienceDaily. ScienceDaily, 9 May 2011. <www.sciencedaily.com/releases/2011/05/110509122726.htm>.
Journal of Clinical Investigation. (2011, May 9). Reducing the side effects of a multiple sclerosis drug. ScienceDaily. Retrieved July 30, 2015 from www.sciencedaily.com/releases/2011/05/110509122726.htm
Journal of Clinical Investigation. "Reducing the side effects of a multiple sclerosis drug." ScienceDaily. www.sciencedaily.com/releases/2011/05/110509122726.htm (accessed July 30, 2015).

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