Next-Generation Human Liver Models for Antimalarial Drug Assays

Area of Science:

• Parasitology
• Drug Discovery
• Hepatology

Background:

• Malaria remains a significant global health threat despite advances in prevention and treatment.
• The Plasmodium liver stage is a critical therapeutic target for preventing malaria progression.
• Existing liver-stage antimalarial drugs have severe side effects in individuals with glucose-6-phosphate dehydrogenase deficiency.

Purpose of the Study:

• To review current in vitro hepatic models for evaluating antimalarial drug activity.
• To highlight opportunities and challenges in developing new drugs targeting the Plasmodium liver stage.
• To assess the potential of stem cell-derived hepatic models for antimalarial drug development.

Main Methods:

• Review of existing literature on in vitro hepatic models for malaria research.
• Analysis of stem cell technologies (pluripotent and adult stem cells) for modeling liver-stage malaria.
• Evaluation of current toolboxes for assaying antimalarial drug efficacy and toxicity.

Main Results:

• Current 2D cell culture models lack physiological relevance for drug screening.
• Primary human cells present challenges like variability and limited supply.
• Stem cell-derived hepatic models offer improved physiological relevance for studying liver-stage malaria.

Conclusions:

• Advanced in vitro hepatic models, particularly those derived from stem cells, are essential for effective preclinical antimalarial drug development.
• These models can overcome limitations of traditional methods, enabling better assessment of drug efficacy against the Plasmodium liver stage.
• Further development of these models is crucial for discovering safe and effective treatments for liver-stage malaria.