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Rheumatoid arthritis

Dual inhibitor targets fibroblast metabolism in RA

Nature Reviews Rheumatology volume 19, page 760 (2023)Cite this article

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Fibroblast-like synoviocytes (FLSs) have an aggressive phenotype in rheumatoid arthritis (RA) that is associated with metabolic reprogramming and aberrant glucose and glutamine metabolism. New findings highlight the potential of targeting glycolysis and glutaminolysis in RA through the use a dual inhibitor, compound 28MS (c28MS).

“Our research is based on the hypothesis that targeting both pathways simultaneously could offer a more comprehensive and efficient approach to managing the disease,” explains Monica Guma, co-corresponding author on the study. Single-cell RNA sequencing analysis demonstrated that specific sublining fibroblast subsets in RA express high levels of hexokinase (HK2; a key enzyme in glycolysis) and glutaminase (GLS; a key enzyme in glutaminolysis). Certain genes were only expressed in those cells that expressed both enzymes, including genes related to inflammation and modulation of the extracellular matrix.

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References

Original article

  • Ahmen, S. et al. Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis. Arthritis Res. Ther. 25, 176 (2023)

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  1. Nature Reviews Rheumatology http://www.nature.com/nrrheum/

    Jessica McHugh

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  1. Jessica McHugh
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Correspondence to Jessica McHugh.

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McHugh, J. Dual inhibitor targets fibroblast metabolism in RA. Nat Rev Rheumatol 19, 760 (2023). https://doi.org/10.1038/s41584-023-01051-y

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