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Protecting β-cells in type 1 diabetes

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Cell replacement therapy is an attractive approach to treat type 1 diabetes (T1D), but without immune suppression, autoimmunity would destroy transplanted β-cells. Using a genome-scale CRISPR screen in a mouse model of T1D, Link et al. discover that deletion of Rnls protects β-cells from immune destruction and confers endoplasmic reticulum stress resistance. RNLS is a flavoprotein oxidase to which the FDA-approved monoamine oxidase B inhibitor pargyline binds, as indicated by structure-based modelling. Oral pargyline treatment protected transplanted β-cells in diabetic mice and prevented or delayed diabetes onset in mouse models of T1D.

Nature Reviews Drug Discovery 19, 588 (2020)

References

  1. 1.

    Link, J. et al. Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes. Nat. Metab. https://doi.org/10.1038/s42255-020-0254-1 (2020)

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