16 October 2018

The Australian Institute of Tropical Health and Medicine (AITHM), based at James Cook University, is an Australian Research Council Special Research Initiative which received $42 million in funding over four years from 2014, to pursue a multi-disciplinary health and tropical medicine program in tropical northern Queensland. 

Professor Alex Loukas is a researcher based at the AITHM whose research team is investigating the secretions of parasitic worms, common in tropical regions of the world, and their possible application in treating autoimmune diseases. In recent years, Professor Loukas’ research has focussed on the secretions of hookworms and their effects on dampening human immune responses.

“My entire research career since 1990 has focussed on parasitic worms, and developing vaccines against them, however in recent years I have made a conscious decision to change my focus to their possible therapeutic uses,” says Professor Loukas.

In August 2018, Professor Loukas’ team announced a $6 million injection of funding from the venture capital arm of the multinational pharmaceutical company AbbVie, Brandon Capital’s Medical Research Commercialisation Fund (MRCF), and OneVentures, to establish a new biotech company, Paragen Bio Pty Ltd, that would focus on treating autoimmune diseases. 

“Parasitic worms have always been here with us as we have evolved—and they are exquisitely designed to be invisible to the human immune system, despite (in the case of hookworms) implanting themselves deeply into the wall of the intestine,” says Professor Loukas.

Professor Loukas’ team has discovered that hookworm secretions help to dampen the human body’s immune response, by just the right amount to remain invisible, but not so much that the body becomes dangerously susceptible to other pathogens.

Professor Loukas says that researchers believe that an imbalance between the effector and regulatory arm of the body’s immune system—which results in autoimmune diseases—could sometimes be the result of our clean lifestyles and the absence of parasites, which the human body has evolved to accommodate. This theory is borne out by observations that people in developing countries develop allergies and autoimmune diseases following anti-parasitic treatment at a higher rate than those people who remain infected with worms. 

Professor Loukas and his colleagues have shown that administering a small number of hookworms to patients with gastrointestinal autoimmune diseases, such as coeliac disease, improves tolerance to dietary gluten by boosting the numbers of regulatory immune cells in the gut.

“We have found that, hookworm secretions (saliva) are useful for supressing all sorts of immune diseases in animal models, including inflammatory bowel disease and asthma. Using secretions has shown us that you don’t need the worm. We have identified a family of lead therapeutic proteins within the saliva, and the goal now is to understand how they exert their anti-inflammatory properties, and produce them in recombinant form using standard pharmaceutical industry approaches,” says Professor Loukas.

Through Paragen Bio, the researchers are now taking their lead candidates to the stage where they are ‘clinic ready’—a process that they hope to be completed in about two years. They will also be carefully screening more than 200 proteins known to be present in hookworm secretions for their anti-inflammatory properties, a guided approach that Professor Loukas contrasts with the lottery of older “grind and find” methods.

“We have advanced our research to this current stage thanks to ARC funding through Linkage Infrastructure Equipment and Facilities scheme grants, and particularly through the AITHM which has given us fantastic facilities—the building I’m sitting in was built using AITHM funds,” says Professor Loukas.

Now with investors attracted to the significant commercial applications of the research, and with the real prospect of anti-inflammatory pharmaceutical products appearing in the not-too-distant future, Professor Loukas says that it is an exciting time.

“Autoimmune diseases are reaching epidemic proportions in developed countries and there is an urgent need for new therapeutic approaches,” says Professor Loukas. “Industry investment through our AITHM spin-off Paragen Bio will help us make that critical step from fundamental research towards developing a potential treatment.”

Images: A hookworm head under an electron microscope. Hookworms in a petri dish. Credit: Alex Loukas.