For years, Distinguished Professor Alex Loukas from the Australian Institute of Tropical Health and Medicine (AITHM) has been hunting for a vaccine against hookworms, a parasitic infection that affects more than 740 million people worldwide. However, more recently, his research has found that these parasites might actually offer a benefit: certain proteins found in hookworm saliva could be used to treat inflammatory bowel disease (IBD) and other autoimmune diseases.
Hookworms are small parasitic worms that live in the soil in countries with a warm and humid climate. Hookworm larvae can break through human skin, and, attached to the walls of the small intestine of dogs, cats and humans, they can survive for years.
Many people who have been infected are feeding millions of hookworms, which leaves them permanently fatigued due to the constant blood loss. “The disease can be treated, but people can be quickly reinfected, sometimes within four to six months,” Professor Loukas said. “This is why it’s important that we find a vaccine.”
However, there is also a positive side to the human-hookworm connection. “Hookworms are really potent at regulating and suppressing inflammation. They are doing this to protect their own existence and hide from our immune system,” Professor Loukas said. “We are now trying to harness that phenomenon and develop an entirely novel approach inspired by nature to treating autoimmune diseases such as IBD.”
Professor Loukas’ colleague at James Cook University (JCU), Dr Paul Giacomin, led a clinical trial where people with metabolic syndrome (precursor to type 2 diabetes) were infected with up to 40 hookworms. Trial volunteers reported a better quality of life and improved insulin sensitivity compared to placebos who did not receive a worm infection.
Some volunteers have been living in partnership with their small band of hookworms for years. But Professor Loukas knows that not everyone enjoys the thought of permanently hosting hookworms in their gut. This is why he and Dr Giacomin are using their knowledge about hookworm proteins to develop novel medications via their startup biotech company, Macrobiome Therapeutics Pty Ltd.
“Our research has found that a single protein from our hookworms can prevent the onset of IBD and other inflammatory conditions such as rheumatoid arthritis,” Professor Loukas said.
“We've got a handful of hookworm molecules that we engineer in the laboratory. They have all the right drug-like properties, and that is the reason we formed our company. We have selected two lead candidate molecules, and we're in the phase now that we would refer to as pre-clinical development.
“We have to create a version of our molecules to make them stay in the blood stream for longer,” Professor Loukas said. “We're currently trying to raise funding for this program. If that's successful, we go into clinical development to turn the molecules into a finished product. This is probably going to be a weekly or monthly injection, similar to the diabetes drug Ozempic.”
A vaccine against hookworms is also still on Professor Loukas’ agenda. “We are part of an EU-funded program that is developing vaccines for hookworm and blood fluke, with collaborators in the Netherlands, United Kingdom, Switzerland, Italy and Spain. By working in collaboration with researchers from around the world, we have a better chance of finally developing a vaccine that stops people from getting reinfected.”