Subject collection: Model Systems in Drug Discovery
- 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.
- Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation
Summary: A novel method for isolating and expanding primary neural crest cells, and establishment of reproducible temporal benchmarks of differentiation, provides a potential screening platform for developmental toxicity or therapeutic capacity.
- Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of Caenorhabditis elegans and its functional response to drugs
Editor's choice: Dystrophin-deficient Caenorhabditis elegans have measurably weak muscle strength and mitochondrial dysfunction, and they respond to drug treatments standard in treating human Duchenne muscular dystrophy.
- CRISPR-Cas9 human gene replacement and phenomic characterization in Caenorhabditis elegans to understand the functional conservation of human genes and decipher variants of uncertain significance
Summary: Here, we provide a CRISPR-Cas9 human gene replacement and phenomic characterization strategy to directly replace Caenorhabditis elegans genes with their human orthologs for disease variant modeling and therapeutic screening.