Macrobiome Therapeutics is developing next-generation biologics for treating disorders that result from a dysfunctional immune system. Our drug discovery ethos is underpinned by millennia of host-parasite co-evolution. Parasitic worms have evolved to survive in their vertebrate hosts while causing minimal pathology, a relationship that has been fine tuned for millions of years. We are harnessing the therapeutic potential of parasites to develop the next generation of biologics inspired by nature”.
Inflammatory Bowel Disease (IBD)
This paper details the biodiscovery pipeline used to identify novel anti-inflammatory drug leads from the dog hookworm secretome. A high-throughput screen was used to filter the 91 candidate proteins for efficacy in a mouse model of IBD(colitis), and positive “hits” were screened for immunosuppressive activity against human IBD patient gut immune cells, identifying 4 promising new leads for colitis.
Describes the discovery and pre-clinical testing of a novel recombinant protein treatment for colitis in mice. This protein called Na-AIP-1, derived from the human hookworm Necator americanus, could suppress acute and chronic models of colitis in mice, and suppress inflammatory cytokine secretion by human T cells.
Examines the protective efficacy of a recombinant protein from the canine hookworm Ancylostoma caninum (AIP-1) in a mouse model of colitis. AIP-1 treatment was efficacious at reducing disease severity and suppressed intestinal pro inflammatory cytokine responses.
This study demonstrates that treatment of mice with natural, crude mixtures of hookworm excretory-secretory(ES) proteins is effective at reducing disease in a mouse model of colitis.
Type 2 Diabetes
This paper shows that treatment with a rodent hookworm species is able to improve metabolic health in mice fed a Type 2 diabetes-inducing high fat diet or a high carbohydrate diet. Protection from disease was associated with induction of a Type 2 immune response and expansion of eosinophils and alternatively-activated macrophages.
This study demonstrates that the beneficial effects of live hookworms in mouse models of Type 2 diabetes can be recapitulated by treatment with worm excretory secretory proteins alone.
This study describes how the bioactive region of a wound healing granulin protein derived from the liver fluke Opisthorchis viverrini was identified, and produced as a peptide product. The peptide was highly potent at promoting human cell prolife ration and healing wounds in a mouse model-therefore representing a more convenient to produce and less immunogenic product for healing wounds than the full-length granulin protein.
Other inflammatory Diseases
This study reports the suppression of asthma in mice by a novel recombinant protein derived from the canine hookworm Ancylostoma caninum(AIP-2). AIP2 was shown to have a distinct mechanism of action involving interactions with tolerogenic dendritic cells and expansion of regulatory T cells.
Details the efficacy of the hookworm protein Na-AIP-1, which was previously shown to be protective in IBD, in a mouse model of collagen-induced arthritis, when delivered as a monotherapy or in combination with methotrexate.
A review article that summarises the state of the literature and future prospects regarding helminth product-derived treatments for a range of inflammatory and metabolic diseases.