TY - JOUR T1 - Repurposing miltefosine for the treatment of immune mediated disease? JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.113.212654 SP - jpet.113.212654 AU - Auke P Verhaar AU - Manon E Wildenberg AU - Maikel P Peppelenbosch AU - Daniel W Hommes AU - Gijs R van den Brink Y1 - 2014/01/01 UR - http://jpet.aspetjournals.org/content/early/2014/05/15/jpet.113.212654.abstract N2 - Miltefosine is an ether lipid initially developed for cancer treatment in the early eighties. Miltefosine largely failed development for oncology although it has been approved for the topical treatment of breast cancer metastasis. It was subsequently discovered that miltefosine is a highly effective treatment for visceral Leishmaniasis, a parasitic disease which affects millions worldwide and causes an estimated 30.000 fatalities each year. Oral treatment with miltefosine is in general well tolerated and has relatively few adverse effects. The exact mechanism of action of miltefosine treatment is still a matter of 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 is currently available for therapeutic use. ER -