Chemotherapy of Leishmania and Trypanosoma Infections: Lost in Translation?
Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19226
Interests: Leishmania; Trypanosoma; chemotherapy; immunology; pathophysiology; pharmacology; parasites; vaccination; dog; ruminants; translational therapeutics; new drugs; drug delivery systems
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Infections by the kinetoplastidsTrypanosoma and Leishmania are widespread, causing debilitating or deadly processes and affecting a variety of hosts, including humans. Some species are zoonotic and both domestic and wild hosts can be infected, providing uncontrolled infection reservoirs. Naturally occurring vectoral transmission makes the environmental control virtually unfeasible in most cases; vaccination is unavailable or very limited, and the reduction of infection level and its extension relies mainly on chemotherapy. The therapeutic arsenal is very limited and of variable efficacy depending on the kinetoplastid species involved or even the developmental stage. Most of the available drugs have toxicity issues and with few exceptions were synthesized over 50 years ago. Very few new chemical entities (NCE) are foreseen, and resistance to the commonly used drugs has been increasingly been reported. Exploratory studies are largely carried out by academia given the low revenues expected by industry. Strategies to cope with the shortage of NCE include the development of drug delivery systems, combination of available drugs, and target-based exploration combined with high-throughput drug screening. Insofar, current therapeutics involves, as a rule, the same compounds available along the second half of the 20th century.
Reports on the identification of new targets in the parasites and new molecules of potential value are abundant. However, the effective progress of these molecules along the drug pipeline has been negligible. Several causes for the scarcity of NCE and the high attrition rate of the candidates could be invoked. Among them, the inherent difficulty involved, the complexity of life cycles or the inadequate surrogate models for drug screening have been incriminated. There are other issues receiving lower consideration that could be relevant to reduce the high numbers of molecules of potential values never tested in adequate models or “drug killing” in the so-called Valley of Death in drug discovery.
Potential topics for this issue include, but are not restricted to, research papers or reviews on pharmacology-driven selection of molecules for the treatment of Leishmania and Trypanosoma infections, knowledge of pathophysiology of the diseases and its effect on drug availability and efficacy, improvement of the identification of predictive markers of efficacy, drug delivery systems and their value beyond laboratory, standardization of efficacy trials, relative value of in vitro, ex vivo and in vivo models for drug exploration, impact of microbiome on efficacy, immune modulation to improve drug efficacy, and strategies to minimize drug resistance emergence and extension.
Therapy of these life-threatening human and animal diseases is challenging, but the reward is high. I hope you find the topic attractive and that your contribution can help to develop effective and affordable drugs.
Prof. Dr. José Ma. Alunda
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- high-throughput systems
- target-based drug selection
- in vitro
- in vivo
- ex vivo
- animal models