Leishmaniases: Strategies in treatment development

被引:0
|
作者
Majoor, Alissa [1 ]
Michel, Gregory [1 ]
Marty, Pierre [1 ,2 ]
Boyer, Laurent [1 ]
Pomares, Christelle [1 ,2 ]
机构
[1] Univ Cote Azur, Ctr Mediterraneen Med Mol C3M, INSERM, U1065, BP 23194, F-06204 Nice 3, France
[2] Hop Archet, Ctr Hosp Univ Nice, Serv Parasitol Mycol, CS 23079, F-06202 Nice 3, France
关键词
Treatments; Leishmaniases; Immunomodulator; Ethnopharmacology; DRUG-DELIVERY SYSTEM; VISCERAL LEISHMANIASIS; AMPHOTERICIN-B; IN-VITRO; ANTILEISHMANIAL ACTIVITY; PENTAVALENT ANTIMONY; ANTIPROTOZOAL ACTIVITY; SODIUM STIBOGLUCONATE; ESSENTIAL OIL; AMAZONENSIS;
D O I
10.1051/parasite/2025009
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Leishmaniases are vector-borne parasitic diseases that pose a threat to over 1 billion people worldwide. The parasites target cells of the reticulohistiocytic system, such as macrophages, where they replicate. The disease manifests in various forms, ranging from localized cutaneous leishmaniasis to life-threatening visceral forms, which are fatal in 95% of cases without treatment. Current treatments rely on the invasive administration of toxic and expensive drugs that are increasingly encountering resistance. Therefore, finding alternative treatments for this disease is imperative. This literature review focuses on recent advancements in alternative treatments and aims to present the various strategies designed to address current limitations, including cost, toxicity, off-target effects, administration routes, and the emergence of drug resistance. Starting with an overview of the existing approved treatments and their specific limitations, we categorize treatment development strategies into five key sections: (i) combination therapies using existing approved treatments to enhance efficacy and reduce resistance; (ii) nanoparticle formulations, which enable targeted delivery to infected organs and improved therapeutic efficiency; (iii) drug repositioning, a strategy that has already contributed to the approval of over half of current therapeutic compounds; (iv) immunomodulation, used in conjunction with standard chemotherapies to enhance treatment efficacy and lower relapse rates; and (v) ethnobotanicals, which have demonstrated promising in vitro results by combining low toxicity, immunomodulatory properties, and potent anti-parasitic effects. In summary, this review outlines current strategies in treatment development, emphasizing their advantages over conventional therapies while acknowledging their limitations. Les leishmanioses sont des maladies parasitaires & agrave; transmission vectorielle qui menacent plus d'un milliard de personnes dans le monde. Les parasites ciblent les cellules du syst & egrave;me r & eacute;ticulohistiocytaire, comme les macrophages, o & ugrave; ils se r & eacute;pliquent. La maladie se manifeste sous diverses formes, allant de la leishmaniose cutan & eacute;e localis & eacute;e aux formes visc & eacute;rales potentiellement mortelles, qui sont responsables de d & eacute;c & egrave;s dans 95% des cas sans traitement. Les traitements actuels reposent sur l'administration invasive de m & eacute;dicaments toxiques et co & ucirc;teux qui rencontrent de plus en plus de r & eacute;sistances. Il est donc imp & eacute;ratif de trouver des traitements alternatifs pour cette maladie. Cette revue de la litt & eacute;rature se concentre sur les avanc & eacute;es r & eacute;centes en mati & egrave;re de traitements alternatifs et vise & agrave; pr & eacute;senter les diff & eacute;rentes strat & eacute;gies con & ccedil;ues pour rem & eacute;dier aux limitations actuelles, notamment le co & ucirc;t, la toxicit & eacute;, les effets hors cible, les voies d'administration et l'& eacute;mergence de la r & eacute;sistance aux m & eacute;dicaments. En commen & ccedil;ant par un aper & ccedil;u des traitements approuv & eacute;s existants et de leurs limitations sp & eacute;cifiques, nous classons les strat & eacute;gies de d & eacute;veloppement de traitements en cinq sections cl & eacute;s : (i) les th & eacute;rapies combin & eacute;es utilisant les traitements approuv & eacute;s existants pour am & eacute;liorer l'efficacit & eacute; et r & eacute;duire la r & eacute;sistance; (ii) les formulations de nanoparticules, qui permettent une administration cibl & eacute;e aux organes infect & eacute;s et une efficacit & eacute; th & eacute;rapeutique am & eacute;lior & eacute;e; (iii) le repositionnement des m & eacute;dicaments, une strat & eacute;gie qui a d & eacute;j & agrave; contribu & eacute; & agrave; l'approbation de plus de la moiti & eacute; des compos & eacute;s th & eacute;rapeutiques actuels; (iv) l'immunomodulation, utilis & eacute;e en conjonction avec les chimioth & eacute;rapies standard pour am & eacute;liorer l'efficacit & eacute; du traitement et r & eacute;duire les taux de rechute; (v) les produits ethnobotaniques, qui ont d & eacute;montr & eacute; des r & eacute;sultats in vitro prometteurs en combinant une faible toxicit & eacute;, des propri & eacute;t & eacute;s immunomodulatrices et un puissant effet antiparasitaire. En r & eacute;sum & eacute;, cette revue d & eacute;crit les strat & eacute;gies actuelles de d & eacute;veloppement de traitements, en soulignant leurs avantages par rapport aux th & eacute;rapies conventionnelles tout en reconnaissant leurs limites.
引用
收藏
页数:17
相关论文
共 50 条
  • [1] Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases
    Lanza, Juliane S.
    Pomel, Sebastien
    Loiseau, Philippe M.
    Frezard, Frederic
    EXPERT OPINION ON DRUG DELIVERY, 2019, 16 (10) : 1063 - 1079
  • [2] Development of miltefosine for the leishmaniases
    Berman, JD
    MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2006, 6 (02) : 145 - 151
  • [3] IMMUNOLOGY AND TREATMENT OF THE LEISHMANIASES
    DAVIDSON, RN
    KONECNY, P
    CURRENT OPINION IN INFECTIOUS DISEASES, 1995, 8 (05) : 336 - 341
  • [4] ENDEMIC DISEASE AND DEVELOPMENT - THE LEISHMANIASES
    WIJEYARATNE, PM
    ARSENAULT, LKJ
    MURPHY, CJ
    ACTA TROPICA, 1994, 56 (04) : 349 - 364
  • [5] Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases
    Monteiro, Lis Marie
    Lobenberg, Raimar
    Cotrim, Paulo Cesar
    Barros de Araujo, Gabriel Lima
    Bou-Chacra, Nadia
    BIOMED RESEARCH INTERNATIONAL, 2017, 2017
  • [6] Liposomal Amphotericin B Treatment and the Leishmaniases
    Berman, Jonathan
    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2019, 101 (04): : 727 - 728
  • [7] Treatment of New World cutaneous and mucosal leishmaniases
    Berman, JD
    CLINICS IN DERMATOLOGY, 1996, 14 (05) : 519 - 522
  • [8] THE LEISHMANIASES
    不详
    WHO TECHNICAL REPORT SERIES, 1984, (701) : 9 - 140
  • [9] LEISHMANIASES
    MUTINGA, MJ
    INSECT SCIENCE AND ITS APPLICATION, 1986, 7 (03): : 421 - 427
  • [10] INTERACTIONS BETWEEN IMMUNITY AND CHEMOTHERAPY IN THE TREATMENT OF THE TRYPANOSOMIASES AND LEISHMANIASES
    BERGER, BJ
    FAIRLAMB, AH
    PARASITOLOGY, 1992, 105 : S71 - S78