Discussion

Hookworms possess potent immunoregulatory properties. Support for this notion comes from immuno-epidemiological observations in hookworm-endemic countries, clinical trials involving experimental infection of volunteers with hookworms, and studies with animal models of inflammatory diseases. As proof-of-concept for the therapeutic benefits of helminth therapy, we have completed a small open label clinical trial using trace gluten consumption coupled with hookworm as an immunoregulatory agent to treat coeliac disease. Beyond our expectations, the treatment resulted in improved gluten tolerance, improved coeliac disease activity measurements and increased regulatory T cell (Treg) numbers in the intestinal epithelium. Despite the promising efficacy of live helminth therapy, the approach has major drawbacks for wide-spread implementation. Central to the hookworm's ability to modulate inflammation is the excretory/secretory (ES) component, the parasite's public face of the host-pathogen interactome. We have characterised the hookworm secretome using genomics and targeted proteomics of the ES proteins and secreted vesicles. At least one family of abundant ES proteins with therapeutic properties in mouse models of asthma, colitis and rheumatoid arthritis has been identified, and one of these proteins (AIP-2) is undergoing further development in partnership with pharma as a novel biologic for treating autoimmune diseases.