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A topical nitric oxide-generating therapy for cutaneous leishmaniasis
R N Davidson1, V Yardley, S L Croft
1Department of Infection and Tropical Medicine, Northwick Park Hospital, Harrow, UK. r.n.davidson@ic.ac.uk
Transactions of the Royal Society of Tropical Medicine and Hygiene
|September 7, 2000
Summary
Topical nitric oxide (NO) generating creams showed limited success in treating cutaneous leishmaniasis (CL). While effective in vitro, clinical trials demonstrated low cure rates for this Leishmania infection.
Area of Science:
- Immunology
- Parasitology
- Dermatology
- Drug Development
Background:
- Macrophages synthesize nitric oxide (NO), a substance lethal to Leishmania parasites.
- NO's ability to diffuse into tissues suggests potential for topical therapeutic applications.
- Cutaneous leishmaniasis (CL) is a parasitic skin infection requiring effective treatments.
Purpose of the Study:
- To investigate the efficacy of topical nitric oxide (NO)-generating creams for treating cutaneous leishmaniasis (CL).
- To explore non-enzymatic generation of NO using nitrite acidification for potential therapeutic use.
- To assess the safety and effectiveness of NO-generating creams in preclinical and clinical settings.
Main Methods:
- Nitric oxide (NO) was generated non-enzymatically by combining potassium nitrite (KNO2) with ascorbic acid (ASC) or salicylic acid (SAL).
- In vitro studies evaluated the efficacy of NO-generating combinations against Leishmania major promastigotes and amastigotes, assessing toxicity to macrophages.
- In vivo studies involved topical application of NO-generating creams to L. major-infected mouse models and a clinical trial with 40 CL patients.
Main Results:
- In vitro experiments demonstrated dose- and time-dependent killing of Leishmania parasites by KNO2 combined with SAL, ASC, or KCl, with toxicity observed at higher concentrations.
- Topical application in mice showed modest efficacy in treating L. major CL lesions.
- Clinical trial results in 40 patients showed low efficacy, with only 28% improving and 12% cured after 4 weeks of treatment.
Conclusions:
- Topical NO-generating creams exhibit limited therapeutic potential for cutaneous leishmaniasis based on current formulations and trial results.
- Further research and development are necessary to optimize NO-generating cream formulations for improved efficacy and safety in treating CL.
- The study highlights the need for continued investigation into novel and effective treatments for Leishmania infections.