Anti-inflammatory molecule could unlock new treatments for severe asthma
Asthma is a very common condition and, while it’s treatable, there’s always a need for new options. Researchers at Trinity College Dublin have now found that an inflammatory “off switch” molecule could help treat severe asthma.
The characteristic shortness of breath in asthma sufferers is caused by inflammation of the airways. Essentially, it’s an overactivation of the immune system in response to allergens like dust, smoke, pollution or other triggers.
Past research has homed in on a protein called JAK1, which plays a key role in driving immune responses by signaling for immune cells called macrophages to patrol for foreign bodies. As important as it is, sometimes JAK1 can get a little overzealous and stimulate macrophages excessively, creating inflammation. This can manifest in a range of conditions, such as Crohn’s disease, rheumatoid arthritis and asthma, and JAK inhibitors are emerging as potential treatments for these.
In the new study, the Trinity researchers identified a JAK inhibitor produced by our own bodies. The molecule, known as itaconate, has previously been found to function as a kind of off-switch for inflammation by putting the brakes on the overactive macrophages. It turns out that it also acts on JAK1, and together these modes of shutting down inflammation seem to help against asthma.
The researchers tested an itaconate derivative called 4-OI on mouse models of severe asthma, which doesn’t respond to the usual anti-inflammatory steroid treatments. The molecule was found to decrease activation of JAK1 and reduce the severity of asthma in the mice.
“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,” said Dr. Marah Runtsch, lead author of the study.
The research was published in the journal Cell Metabolism.
Source: Trinity College Dublin