Subject collection: Model Systems in Drug Discovery
- Integrating fish models in tuberculosis vaccine development
Summary: In this Review, we discuss how zebrafish (Danio rerio) and other fish models can complement the more traditional mammalian models in the development of novel vaccines against tuberculosis.
- Neuromuscular disease modeling on a chip
Summary: Modeling neuromuscular diseases is challenging due to their complex etiology and pathophysiology. Here, we review the cell sources and tissue-engineering procedures that are being integrated as emerging neuromuscular disease models.
- Precision-based modeling approaches for necrotizing enterocolitis
Summary: Much of our understanding of necrotizing enterocolitis (NEC) pathogenesis has been achieved through animal models. Here, we discuss the development of advanced precision-based models to improve outcomes for patients with NEC.
- Mouse models for muscular dystrophies: an overview
Summary: This Review and its accompanying comprehensive table summarize the most commonly used mouse models for a subset of highly studied muscular dystrophies.
- Improving translatability of preclinical studies for neuromuscular disorders: lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT)
Summary: Rigorous preclinical efficacy studies de-risk clinical trials in neuromuscular diseases. This Review summarizes the impact of expert panel advice on translational studies.
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG
Editor's choice: Drug repurposing screens using worm and patient fibroblast models of PMM2-CDG led to the discovery of epalrestat, the first activator of PMM2 that targets the root cause of disease.
- Drug screens of NGLY1 deficiency in worm and fly models reveal catecholamine, NRF2 and anti-inflammatory-pathway activation as potential clinical approaches
Summary: Using worm and fly models of an ultra-rare congenital disorder of glycosylation, we performed repurposing screens and identified the FDA-approved drug aripiprazole as a clinical candidate.
- Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns
Summary: Large-scale, focused phenotyping campaigns provide data for thousands of mutant mouse genes, yielding key information for understanding rare human diseases and for developing novel drug therapies.
- A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects
Editor's choice: Mitochondria are conserved among eukaryotes and mutations in the factors that control their dynamics are causal for various human disorders. Hence, yeast models can be used for pharmacological screenings.
- Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
Summary: Using the vps13Δ strain, a yeast model of the neurodegenerative disorder chorea-acanthocytosis, we found that its defects can be overcome by reduction of calcineurin activity and/or type-I-myosin activation.