Helminth-derived products for type 2 diabetes

Background

Obesity, insulin resistance and type 2 diabetes (T2D) are rising at an alarming rate affecting almost 400 million people worldwide and expected to rise to 600 million by 2035. Although pharmacological treatments are currently available for T2D and its associated metabolic disorders, new innovative strategies are still needed for providing alternatives to progressive drug resistance to conventional medicines. Recent landmark studies have shown that type-2 immune responses are associated with improved insulin sensitivity and glucose homeostasis.This is supported by the ability of parasitic helminths, the strongest natural stimuli of type-2 responses, to improve insulin sensitivity and glucose homeostasis in rodent models of insulin resistance.

Project description

Over the past year, it has been shown that helminth-derived molecules can also improve insulin sensitivity, which indicates that the beneficial effects of helminths on whole-body metabolic homeostasis is mediated by their intrinsic (immuno)modulatory properties rather than “parasitism” on caloric intake. Interestingly, helminth soluble egg antigens (SEA) and a structurally related synthetic polyvalent Lewis X glycoconjugate, were recently shown to improve glucose tolerance and insulin sensitivity in obese mice not only by immune-dependent mechanisms but also by directly modulating lipid metabolism in hepatocytes. In this project we will investigate whether glycoproteins from the human parasite Schistosoma mansoni can be produced in Nicotiana benthamiana plants with a tailored native glycan composition and whether these engineered glycoproteins are able to improve insulin sensitivity and metabolic homeostasis in mice.