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Subject collection: Model Systems in Drug Discovery

  • REVIEW
    Precision-based modeling approaches for necrotizing enterocolitis
    Mark L. Kovler, Chhinder P. Sodhi, David J. Hackam
    Disease Models & Mechanisms 2020 13: dmm044388 doi: 10.1242/dmm.044388 Published 24 June 2020

    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.

  • REVIEW
    Mouse models for muscular dystrophies: an overview
    Maaike van Putten, Erin M. Lloyd, Jessica C. de Greef, Vered Raz, Raffaella Willmann, Miranda D. Grounds
    Disease Models & Mechanisms 2020 13: dmm043562 doi: 10.1242/dmm.043562 Published 21 February 2020

    Summary: This Review and its accompanying comprehensive table summarize the most commonly used mouse models for a subset of highly studied muscular dystrophies.

  • REVIEW
    Improving translatability of preclinical studies for neuromuscular disorders: lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT)
    Raffaella Willmann, Joanne Lee, Cathy Turner, Kanneboyina Nagaraju, Annemieke Aartsma-Rus, Dominic J. Wells, Kathryn R. Wagner, Cristina Csimma, Volker Straub, Miranda D. Grounds, Annamaria De Luca
    Disease Models & Mechanisms 2020 13: dmm042903 doi: 10.1242/dmm.042903 Published 7 February 2020

    Summary: Rigorous preclinical efficacy studies de-risk clinical trials in neuromuscular diseases. This Review summarizes the impact of expert panel advice on translational studies.

  • RESEARCH ARTICLE
    Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG
    Sangeetha Iyer, Feba S. Sam, Nina DiPrimio, Graeme Preston, Jan Verheijen, Kausalya Murthy, Zachary Parton, Hillary Tsang, Jessica Lao, Eva Morava, Ethan O. Perlstein
    Disease Models & Mechanisms 2019 12: dmm040584 doi: 10.1242/dmm.040584 Published 11 November 2019

    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.

  • RESEARCH ARTICLE
    Drug screens of NGLY1 deficiency in worm and fly models reveal catecholamine, NRF2 and anti-inflammatory-pathway activation as potential clinical approaches
    Sangeetha Iyer, Joshua D. Mast, Hillary Tsang, Tamy P. Rodriguez, Nina DiPrimio, Madeleine Prangley, Feba S. Sam, Zachary Parton, Ethan O. Perlstein
    Disease Models & Mechanisms 2019 12: dmm040576 doi: 10.1242/dmm.040576 Published 4 November 2019

    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.

  • SPECIAL ARTICLE
    Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns
    Robert Brommage, David R. Powell, Peter Vogel
    Disease Models & Mechanisms 2019 12: dmm038224 doi: 10.1242/dmm.038224 Published 7 May 2019

    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.

  • RESEARCH ARTICLE
    A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects
    Thomas Delerue, Déborah Tribouillard-Tanvier, Marlène Daloyau, Farnoosh Khosrobakhsh, Laurent Jean Emorine, Gaëlle Friocourt, Pascale Belenguer, Marc Blondel, Laetitia Arnauné-Pelloquin
    Disease Models & Mechanisms 2019 12: dmm036558 doi: 10.1242/dmm.036558 Published 7 February 2019

    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.

  • RESEARCH ARTICLE
    Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
    Piotr Soczewka, Damian Kolakowski, Iwona Smaczynska-de Rooij, Weronika Rzepnikowska, Kathryn R. Ayscough, Joanna Kaminska, Teresa Zoladek
    Disease Models & Mechanisms 2019 12: dmm036830 doi: 10.1242/dmm.036830 Published 28 January 2019

    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.

  • RESOURCE ARTICLE
    Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation
    Maria R. Replogle, Virinchipuram S. Sreevidya, Vivian M. Lee, Michael D. Laiosa, Kurt R. Svoboda, Ava J. Udvadia
    Disease Models & Mechanisms 2018 11: dmm035097 doi: 10.1242/dmm.035097 Published 12 December 2018

    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.

  • RESEARCH ARTICLE
    Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of Caenorhabditis elegans and its functional response to drugs
    Jennifer E. Hewitt, Amelia K. Pollard, Leila Lesanpezeshki, Colleen S. Deane, Christopher J. Gaffney, Timothy Etheridge, Nathaniel J. Szewczyk, Siva A. Vanapalli
    Disease Models & Mechanisms 2018 11: dmm036137 doi: 10.1242/dmm.036137 Published 4 December 2018

    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.

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