Preventing asthma attacks with the unexpected help of worms

It may sound strange, but a protein from a parasitic worm can significantly reduce the risk of an asthma attack. Scientists in Australia have demonstrated this in mouse models. Does this pave the way for a new asthma medication?

Parasitic worms as allies against asthma

About fifteen years ago, it was suspected that parasitic worms could suppress asthma. In tropical countries infections by various worm parasites are still common. Strikingly enough in those regions, fewer children suffer from asthma. Scientists suspected that there was a direct relation to the 'tool box’of these worm parasites.

To find out more about how these worms work, top international scientists joined forces in 2018 within the international Asthma Prevention Program, initiated by Longfonds.

Proteins

Professor Rick Maizels from the University of Glasgow provided evidence that parasitic worms protect children from allergies. 'Our immune system is very effective at attacking parasites. But parasitic worms have developed a trick to survive. They secrete around two thousand different proteins, which suppress the human immune system.’ The side effect of this trick is that inflammatory reactions to allergenic substances are also suppressed. A nice bonus!'

Preventing an asthma attack

But which of these two thousand worm proteins play a key role in that immune response? In 2022, Dr. Henry McSorley of the University of Dundee identified two substances that block an asthmatic reaction: HpARI and HpBARI. These molecules suppress the immune protein IL-33, which in some cases triggers such a strong immune response that people with asthma can have an asthma attack.

Further research

To understand how the worm molecule HpARI works in an immune response, Henry McSorley collaborated with a laboratory in Australia.

This laboratory has developed a unique model in which researchers can investigate the development and effects of childhood asthma. Just like in people with asthma, cold viruses, such as the rhinovirus, cause symptoms in the mouse models. McSorley and the Australian research team suspected that the immune protein IL-33 plays a significant role in this. The question was: what happens to that intense immune response to a virus when you administer the worm molecule HpARI?

Results

The results of the tests proved to be extremely promising. The worm molecule HpARI attached to the immune protein IL-33, thus blocking its function. The immune response, which normally triggers an asthma attack, became much less severe. The results suggest that blocking the immune protein IL-33 can help reduce the severity of asthma attacks.

A new medication with worm protein?

The results prove that the discovery of the worm molecule HpARI can be very interesting in the treatment of people with asthma. McSorley said, 'It shows that the protein we have identified is very effective in this model. And also, if you give people with asthma a medication that blocks the immune protein IL-33, it is likely to prevent asthma attacks. The quality of life for people with asthma will improve, and the condition will become less dangerous.'

Medications for asthma based on natural (human or animal) proteins are called biologicals. These medications inhibit the action of inflammatory substances or immune cells in people with severe asthma. IL-33 could also be inhibited with biologicals.

Other research

Clincal testing of medication typically takes five to ten years. Therefore, an asthma medicine with HpARI will take time before it becomes available. Furthermore, there are currently more studies underway with substances that can suppress the immune protein IL-33.

It is not clear which substances will ultimately be the most effective in suppressing IL-33. But the research into the mechanism of action of the worm molecule HpARI is definitely not in vain; this methodology can also be crucial for other future medications.

Text: Marlijn Klerk