ArticleDisease models & mechanisms2025
Label-free morphology-based phenotypic analysis of spinal and bulbar muscular atrophy muscle cell models.
Article in Disease models & mechanisms, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by CAG trinucleotide expansion in the androgen receptor (AR) gene. To improve the quality of in vitro cell-based assays for the evaluation of potential drug candidates for SBMA, we developed a morphology-based phenotypic analysis for a muscle cell model of SBMA that involves multiparametric morphological profiling to quantitatively assess the therapeutic effects of drugs on muscle cell phenotype. The analysis was validated using dihydrotestosterone and pioglitazone, which have been shown to exacerbate and ameliorate the pathophysiology of SBMA, respectively. Gene expression analysis revealed activation of the JNK pathway in the SBMA cells compared to the control cells. Phenotypic analysis revealed the effect of naratriptan, a JNK inhibitor, on the phenotypic changes of SBMA cells, and the results were confirmed by LDH assays. We then trained a predictive machine learning model to classify the drug responses, and it successfully discriminated between pioglitazone-type and naratriptan-type morphological profiles based on their morphological characteristics. Our morphology-based phenotypic analysis provides a noninvasive and efficient screening method to accelerate the development of therapeutics for SBMA.
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