title: Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis.
abstract: BACKGROUND
  Cutaneous leishmaniasis (CL) represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC) is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains.
  
  
  RESULTS
  The potential of OlPC against Old World CL was evaluated in a mouse model of Leishmania (L.) major infection in BALB/c mice. Initial dose-response experiments showed that an oral daily dose of 40 mg/kg of OlPC was needed to impact time to cure and lesion sizes. This dose was then used to directly compare the efficacy of OlPC to the efficacy of the antileishmanial drugs miltefosine (40 mg/kg/day), fluconazole (160 mg/kg/day) and amphotericin B (25 mg/kg/day). OlPC, miltefosine and fluconazole were given orally for 21 days while amphotericin B was administered intraperitoneally for 10 days. Ulcer sizes and animal weights were followed up on a weekly basis and parasitemia was determined by means of a real-time in vivo imaging system which detects luminescence emitted from luciferase-expressing infecting L. major parasites. Amphotericin B and OlPC showed excellent efficacy against L. major lesions in terms of reduction of parasitic loads and by inducing complete healing of established lesions. In contrast, treatment with miltefosine did not significantly affect parasitemia and lesion sizes, while fluconazole was completely ineffective at the dose regimen tested.
  
  
  CONCLUSIONS
  Given the data showing the outstanding efficacy and tolerability of OlPC, our results suggest that OlPC is a promising new drug candidate to improve and simplify current clinical management of L. major CL.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada; Dafra Pharma Research & Development, Turnhout, Belgium.
authors.forename: Anny
authors.initials: A
authors.lastname: Fortin
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Caridha
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Leed
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Franklyn
authors.initials: F
authors.lastname: Ngundam
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Jenell
authors.initials: J
authors.lastname: Sena
authors.affiliation: Dafra Pharma Research & Development, Turnhout, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Bosschaerts
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Sandi
authors.initials: S
authors.lastname: Parriott
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hickman
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hudson
authors.affiliation: Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Silver Spring, Maryland, United States of America.
authors.forename: Max
authors.initials: M
authors.lastname: Grogl
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects* / Q000494:pharmacology*; D004195:Disease Models, Animal; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010713:Phosphatidylcholines / Q000009:adverse effects* / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D010713:Phosphatidylcholines; D010767:Phosphorylcholine; C039128:miltefosine