Antileishmanial Drug Discovery and Development: Time to Reset the Model?
Ana Isabel Olías-MoleroConcepción de la FuenteMontserrat CuquerellaJuan José TorradoJosé María AlundaPublished in: Microorganisms (2021)
Leishmaniasis is a vector-borne parasitic disease caused by Leishmania species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the Leishmania sp. and the host immune response. No vaccine for humans is available, and the control relies mainly on chemotherapy. However, currently used drugs are old, some are toxic, and the safer presentations are largely unaffordable by the most severely affected human populations. Moreover, its efficacy has shortcomings, and it has been challenged by the growing reports of resistance and therapeutic failure. This manuscript presents an overview of the currently used drugs, the prevailing model to develop new antileishmanial drugs and its low efficiency, and the impact of deconstruction of the drug pipeline on the high failure rate of potential drugs. To improve the predictive value of preclinical research in the chemotherapy of leishmaniasis, several proposals are presented to circumvent critical hurdles-namely, lack of common goals of collaborative research, particularly in public-private partnership; fragmented efforts; use of inadequate surrogate models, especially for in vivo trials; shortcomings of target product profile (TPP) guides.
Keyphrases
- drug discovery
- immune response
- healthcare
- endothelial cells
- drug induced
- locally advanced
- quality improvement
- adverse drug
- insulin resistance
- stem cells
- radiation therapy
- toll like receptor
- mesenchymal stem cells
- type diabetes
- health insurance
- skeletal muscle
- global health
- risk assessment
- inflammatory response
- induced pluripotent stem cells
- bone marrow
- pluripotent stem cells
- chemotherapy induced