People with asthma will often suffer, at varying degrees, from symptoms such as shortness of breath, wheeziness, and bouts of coughing that stem from overactivation of the immune system when exposed to allergens like dust, smoke, and pollution. Many of us may actually remember having asthma as a child but have since outgrown it. After recovering from Covid-19, however, it’s not uncommon for childhood asthma to become reactivated.
While asthma is a common and treatable condition, new and improved treatments are always something to celebrate. This is why we are excited to report that researchers at Trinity College Dublin have identified an inflammatory “off switch” molecule that could effectively treat severe cases of asthma.
The team built on past research that had focused on a protein called JAK1, which plays an important role in driving immune responses by signaling for macrophages (immune cells) to patrol for foreign bodies. This protein, though essential, can sometimes react too fiercely, which then creates unnecessary inflammation. This can lead to conditions like Crohn’s disease, rheumatoid arthritis, and asthma.
One potential solution is a new class of drugs called JAK inhibitors which are comprised of four closely related molecules: JAK1, JAK2, JAK3, and TYK2. In the new study, the Trinity researchers discovered a JAK inhibitor that is naturally produced by our own bodies. This molecule, called itaconate, acts as a sort of off-switch for inflammation by putting the brakes on the overactive macrophages that are stimulated by the overly enthusiastic JAK1. The shutting down of inflammation appears to help against asthma.
So far, the researchers tested an itaconate derivative on mice with severe asthma that previously did not respond to the usual anti-inflammatory steroid treatments. The team found that the molecule decreased activation of JAK1 and was able to reduce the severity of asthma in the mice.
“We have high hopes that new medicines based on itaconate could well have potentially as a wholly new therapeutic approach for treating severe asthma, where there is a pressing need for new treatments,” said the lead author of the study, Dr. Marah Runtsch.
Source study: Cell Metabolism—Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages