Dataset Information

Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis.

ABSTRACT: Tritryps diseases are devastating parasitic neglected infections caused by Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei subspecies. Together, these parasites affect more than 30 million people worldwide and cause high mortality and morbidity. Leishmaniasis comprises a complex group of diseases with clinical manifestation ranging from cutaneous lesions to systemic visceral damage. Antimonials, the first-choice drugs used to treat leishmaniasis, lead to high toxicity and carry significant contraindications limiting its use. Drug-resistant parasite strains are also a matter for increasing concern, especially in areas with very limited resources. The current scenario calls for novel and/or improvement of existing therapeutics as key research priorities in the field. Although several studies have shown advances in drug discovery towards leishmaniasis in recent years, key knowledge gaps in drug discovery pipelines still need to be addressed. In this review we discuss not only scientific and non-scientific bottlenecks in drug development, but also the central role of public-private partnerships for a successful campaign for novel treatment options against this devastating disease.

SUBMITTER: Alcantara LM

PROVIDER: S-EPMC6195035 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis.

Alcântara Laura M LM Ferreira Thalita C S TCS Gadelha Fernanda R FR Miguel Danilo C DC

International journal for parasitology. Drugs and drug resistance 20180928 3

Tritryps diseases are devastating parasitic neglected infections caused by Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei subspecies. Together, these parasites affect more than 30 million people worldwide and cause high mortality and morbidity. Leishmaniasis comprises a complex group of diseases with clinical manifestation ranging from cutaneous lesions to systemic visceral damage. Antimonials, the first-choice drugs used to treat leishmaniasis, lead to high toxicity and carry signifi ...[more]

PMID: 30293058

Similar Datasets

Project description:Novel drugs are needed to treat a variety of persistent diseases caused by intracellular bacterial pathogens. Virulence pathways enable many functions required for the survival of these pathogens, including invasion, nutrient acquisition, and immune evasion. Inhibition of virulence pathways is an established route for drug discovery; however, many challenges remain. Here, we propose the biggest problems that must be solved to advance the field meaningfully. While it is established that we do not yet understand the nature of chemicals capable of permeating into the bacterial cell, this problem is compounded when targeting intracellular bacteria because we are limited to only those chemicals that can permeate through both human and bacterial outer envelopes. Unfortunately, many chemicals that permeate through the outer layers of mammalian cells fail to penetrate the bacterial cytoplasm. Another challenge is the lack of publicly available information on virulence factors. It is virtually impossible to know which virulence factors are clinically relevant and have broad cross-species and cross-strain distribution. In other words, we have yet to identify the best drug targets. Yes, standard genomics databases have much of the information necessary for short-term studies, but the connections with patient outcomes are yet to be established. Without comprehensive data on matters such as these, it is difficult to devise broad-spectrum, effective anti-virulence agents. Furthermore, anti-virulence drug discovery is hindered by the current state of technologies available for experimental investigation. Antimicrobial drug discovery was greatly advanced by the establishment and standardization of broth microdilution assays to measure the effectiveness of antimicrobials. However, the currently available models used for anti-virulence drug discovery are too broad, as they must address varied phenotypes, and too expensive to be generally adopted by many research groups. Therefore, we believe drug discovery against intracellular bacterial pathogens can be advanced significantly by overcoming the above hurdles.

Dataset Information

Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis.

Publications

Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets