An Australian study has identified a protein secreted by parasitic hookworms that suppresses asthma in mice, with in vitro tests on cells from asthmatics indicating that the protein is a promising candidate for development of new anti-inflammatory treatments.

The findings of the study, which was conducted by Australian Institute of Tropical Health and Medicine (AITHM) researchers at James Cook University (JCU) in Cairns, Australia, were published in the Oct. 26, 2016, edition of Science Translational Medicine.

The new study built on previous research into possible treatments for inflammatory bowel disease (IBD), including clinical trials that had established experimental hookworm infection as being an effective anti-inflammatory treatment for celiac disease.

"Over recent years, there has been a trend in developing countries toward improved sanitation and health care access, with the rate of hookworm infections also decreasing, but an increasing incidence of autoimmune and allergic diseases," said Severine Navarro, a senior research fellow in the AITHM Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT) at JCU.

"This observation prompted a group of scientists including Alex Loukas to question why that should be and they discovered the benefits of certain parasites for human health," she told BioWorld Today.

A parasitologist with extensive experience in vaccine development, Loukas is a professor and co-director of the CBMDT, who led the asthma together study with Navarro.

"After our initial success with IBD, asthma was our next logical goal. Although IBD and asthma are very different conditions, they have in common a defect in the regulation of the immune system, whereby the function and efficacy of regulatory T cells in patients with allergies and autoimmune diseases are defective, resulting in overwhelming inflammatory processes," said Navarro.

"The hookworm protein seems to reverse this defect and promote the long-lasting regulation of allergy-type immune responses," she told BioWorld Today. "To survive and remain undetected in the human gut, parasitic worms must regulate their host's immune response. When hookworms infest the gut, they anchor themselves and burrow within the mucosa.

"In order that the host's immune system 'ignores' them, the worms produce compounds that not only locally heal the wound, but also promote regulatory T cells and overall tolerance by antigen-presenting cells to allergens and self-antigens," Navarro said. "We aim to use that process to control the inappropriate inflammation that characterizes autoimmune diseases and allergy."

The AITHM researchers showed that mice treated with the worm protein showed an extensive suppression of inflammatory responses after allergen exposure. A recombinant form of the protein, called AIP-2, was also tested in vitro on human cells from people allergic to dust mites.

"Experimental asthma in mice is similar to the pathogenesis observed in humans," noted Navarro. "In both conditions we see reduced lung function, a massive infiltration of inflammatory cells into the lung, and a significant increase in allergen-specific antibodies, with these parameters being readily quantifiable in the laboratory.

"Our previous work on IBD had established that hookworm proteins can change T cells from [being] pro-inflammatory to anti-inflammatory," Navarro said. "The good news is that this doesn't just protect the gut, it also protects other organs, including the airways."

"This study also represents an important step forward in our exploitation of the therapeutic potential of hookworm proteins," said Loukas, noting that AIP-2 is a promising potential treatment for allergic conditions.

"In our initial work on IBD, we infected trial participants with actual hookworms. We have since established that the protective properties of hookworms lie in their oral secretions. More recently, we've isolated AIP-2, one of the most abundant [anti-inflammatory] proteins in that secretion mixture.

"In the asthma study, we used a recombinant form of AIP-2, which is to say we're now able to reproduce it in large quantities. We treated the mice with it by injection and also intranasally," said Loukas.

"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 due to an imbalance in the ratio of effector to regulatory T cells. These include IBD, multiple sclerosis, rheumatoid arthritis, psoriasis, eosinophilic esophagitis and even food allergies," said Loukas.

"With appropriate partnerships and funding we hope to commence clinical trials within three years," he told BioWorld Today, adding his group's objectives are "to secure the partnerships and funding required to progress to manufacture and clinical trials."

"We are actively looking for the definitive target of the protein, which will allow to safely determine its potential administration in humans," added Navarro. "Ideally, the treatment should be a pill that could be taken over a short time to provide long-term relief against allergies.

"Our next step will be to move the protein toward a phase I clinical trial. We have also developed a high throughput approach to identify any other potential compounds contained in the worm saliva that has anti-inflammatory properties. This will eventually establish a library of potential therapeutics that will hopefully provide the next generation of treatments on the market."