Repurposing miltefosine for the treatment of immune-mediated disease?

J Pharmacol Exp Ther

Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands (A.P.V., M.E.W., G.R.v.d.B.); Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands (A.P.V., D.W.H.); Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands (M.P.P.); and Center for Inflammatory Bowel Diseases, University of California Los Angeles, Los Angeles, California (D.W.H.)

Published: August 2014

Miltefosine is an ether lipid that was initially developed for cancer treatment in the early 1980s. Miltefosine largely failed development for oncology, although it was approved for the topical treatment of breast cancer metastasis. It was subsequently discovered that miltefosine is a highly effective treatment of visceral Leishmaniasis, a parasitic disease that affects millions worldwide and causes an estimated 30,000 fatalities each year. Oral treatment with miltefosine is generally well tolerated and has relatively few adverse effects. The exact mechanism of action of miltefosine treatment is still under investigation. Its close resemblance to phospholipids allows it to be quickly taken up by cell membranes and affect related processes, such as lipid metabolism and signaling through lipid rafts. These processes play an important role in the immune response and it comes as no surprise that miltefosine has been successfully tested for the treatment of a number of immune-mediated diseases in preclinical models of disease. Drug repurposing of miltefosine for immune-mediated diseases may provide an opportunity to expand the limited number of drugs that are currently available for therapeutic use.

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http://dx.doi.org/10.1124/jpet.113.212654DOI Listing

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