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A study by Dr I-Shu Huang and colleagues in Professor Richard Williams’s Group published in PNAS shows that decitabine, a drug currently approved for treatment of cancer patients, can boost regulatory T cells in animal models. As robust regulatory T cells have the capacity to suppress immune-driven inflammation, the findings offer a treatment pathway for chronic inflammatory diseases like rheumatoid arthritis (RA).
Richard said: “RA is characterised by a deficit in fully functional regulatory T cells. But there is evidence that DNA-methylation inhibitors, used for treatment of cancer, increase regulatory T cell responses in patients. This led us to question whether short-term treatment of autoimmune arthritis with DNA methylation inhibitors could restore numbers of regulatory T cells, leading to long-term suppression of disease."
Of three DNA methylation inhibitors tested in an animal model of rheumatoid arthritis, decitabine was the most effective, producing a sustained therapeutic effect. The researchers observed a profound and rapid decrease in numbers of pathogenic Th1 and Th17 cells in decitabine treated mice and an increase in numbers of regulatory T cells, particularly in the inflamed joint.
“This study identifies a path toward resetting tolerance in autoimmune disease using a repurposed drug,” said Richard. “However, decitabine acts in a non-specific way and therefore is likely to have many off-target effects when used in a chronic disease like rheumatoid arthritis. Further research would aim to identify more selective epigenetic drugs to restore immune homeostasis.”