The number of Americans with asthma is rising every year, highlighting the need for new treatments for the respiratory condition. Now, a new study reveals how the quest for new asthma treatments may have been given a helping hand by an unlikely foe: the hookworm.

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Researchers say a protein secreted by hookworms could lead to new treatments for asthma.
Image credit: JCU

Hookworms are intestinal parasites responsible for up to 760 million infections across the globe.

While most people infected with hookworm have no symptoms, some people may experience abdominal pain, diarrhea, loss of appetite, weight loss, fatigue, and anemia.

But according to researchers from James Cook University (JCU) in Australia, hookworms may not be all bad.

Study co-author Dr. Severine Navarro, of the Australian Institute of Tropical Health and Medicine at JCU, and colleagues reveal how a protein secreted by hookworms – anti-inflammatory protein 2 (AIP-2) – curbed airway inflammation in a mouse model of asthma.

The study builds on previous research from the team, which showed that the same protein may be effective for an array of inflammatory conditions, including inflammatory bowel diseases (IBD), such as Crohn’s disease.

“After our initial success with IBD, asthma was our next logical goal,” says Dr. Navarro. “Although IBD and asthma are very different conditions, what they have in common is a defect in the regulation of the immune system, which results in overwhelming inflammatory processes.”

For their latest study – published in the journal Science Translational Medicine – Dr. Navarro tested the AIP-2 protein on mouse models of asthma.

“[…] we used a recombinant form of AIP-2, which is to say we’re now able to produce it in large quantities,” notes study co-author Prof. Alex Loukas, head of the Centre for Biodiscovery and Molecular Development of Therapeutics at JCU.

The team administered the protein to the mice intranasally and through injection, before exposing them to an allergen to trigger the inflammatory response associated with asthma.

The researchers found that AIP-2 suppressed airway inflammation in the mouse models, likely by altering the inflammatory properties of T cells – white blood cells that help fight viruses – in response to the allergen.

“Our previous work on inflammatory bowel disease established that hookworm proteins can change T cells from pro-inflammatory to anti-inflammatory,” explains Dr Navarro. “The good news is that this doesn’t just protect the gut, it also protects other organs, such as the airways, where asthma develops.”

The researchers also applied recombinant AIP-2 to human cells taken from patients with an allergy to dust mites, which is a common trigger for asthma.

They found that the worm protein curbed activation of dendritic cells – antigen-processing cells – and T cells, an indicator of reduced inflammatory response to allergens.

Asthma now affects around 25 million people in the United States, compared with around 20 million in 2001.

The researchers say their findings may lead to new treatments for asthma, as well as other autoimmune conditions, especially now that they have demonstrated the efficacy of recombinant AIP-2.

“This is an exciting development for us, because it means we’re another step closer to being able to put a pill-based treatment into clinical trials, not just for asthma but also for other inflammatory and autoimmune diseases.”

Prof. Alex Loukas

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