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T1D reversed in mice using engineered gut bacteria

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T1D reversed in mice using engineered gut bacteria

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An oral treatment of harmless, specially engineered gut bacteria was able to reverse type 1 diabetes (T1D) in experimental mice, according to a partially JDRF-funded study in Belgium. The findings, which were recently published in the April edition of the Journal of Clinical Investigation, may hold implications for future translation of the treatment to people with the disease, which has no known cause or cure.

The international, collaborative team, led by Chantal Mathieu, M.D. at Belgium’s KU Leuven and ActoGenix, a biopharmaceutical company, treated the mice with ActoBiotic therapy—genetically modified Lactococcus lactis—which secreted an autoantigen called proinsulin, and an immune-modulatory protein molecule called interleukin-10 (IL-10), an anti-inflammatory protein molecule with suppressive effects in preventing autoimmune disease. When combined with a low dose of an anti-CD3 antibody for five days, the therapy halted T1D progression in the newly-diagnosed, non-obese diabetic (NOD) mice. CD3 is a protein required for T-cell activation. T-cells are immune cells that are involved in the destruction of beta cells in the pancreas during the autoimmune process of T1D.

Three months of follow-up after the mice were given the ActoBiotic treatment showed that glucose levels in the mice remained stable. The investigators also reported that while there was no evidence the therapy triggered beta cell proliferation, it did seem to reactivate beta cells that were deactivated by the diabetes-related immune inflammation. The investigators suggested that this combination resulted in a resetting of the immune system toward a long-term tolerance of the body’s beta cells.

The KU Leuven study adds to our understanding of T1D, which is why JDRF is actively supporting research that allows us to better understand the process leading to the misguided immune attack on the beta cells and potential therapeutic interventions at each stage of this complex disease. In particular, JDRF is looking at ways to develop more specific therapies to promote tolerance of the beta cell antigens that trigger the autoimmune response, without generally weakening the immune system; such therapies are a critical component of a comprehensive therapeutic approach to T1D.

  • Wow, what amazing news!  Seems almost too good to be true, but man this would be awesome.

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