A new class of immunotherapy drugs – used to treat arthritis, psoriasis, and inflammatory bowel disease – might also work for those with severe asthma. The pharmaceuticals are known as 'jakinibs' because they inhibit the protein JAK1. This protein plays an essential role in the body's immune response by activating cytokines, which can then lead to inflammation. In cases of asthma, however, the JAK1 protein can cause a cytokine 'storm' to develop in the lung, leading to a level of inflammation that can be life-threatening. By inhibiting JAK1, researchers at Trinity University in Ireland have now shown it's possible to suppress this over-involved immune response with "remarkable efficacy". Whether this can reduce asthmatic symptoms outside the lab remains to be seen, but it's worth investigating further. In the current study, the JAK1 inhibitor used on both humans and animal cells is based on a metabolite called itaconate. Naturally produced by our bodies, the molecule itaconate is already known to play a major role in modifying the behavior of white blood cells. This latest study has uncovered how itaconate and one of its derivatives, 4-octyl itaconate (4-OI) shuts down the JAK1 protein so it can no longer trigger storms of circulating cytokines. "We tested a molecule called 4-OI, which is based on itaconate, and it was able to suppress severe asthma in a model of the disease which doesn't respond to anti-inflammatory steroids," explains immunologist Marah Runtsch. "We have high hopes that new medicines based on Itaconate could well have potential as a wholly new therapeutic approach for treating severe asthma, where there is a pressing need for new treatments." This isn't the first time jakinibs like 4-OI have been proposed as a potential avenue for asthma treatment. There are multiple asthma-associated cytokines that have been linked to the JAK1 protein, and a growing body of preclinical data supports the idea that suppressing JAK1 can reduce airway inflammation by dampening the cytokine response. Just last year, an inhaled jakinib was tested in a double-blinded placebo-controlled trial and was found to reduce symptoms among those with mild asthma. The first generation of jakinibs on the market is still not perfect, but drugmakers are gradually learning to make the medicine more specific and more effective for conditions like arthritis. Asthma could be their next frontier. Source
