Repurposing the FDA-Approved Pinworm Drug Pyrvinium as a Novel Chemotherapeutic Agent for Intestinal Polyposis

Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APC^min mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APC^min mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.     

Assessing European Egg Parasitoids as a Mean of Controlling the Invasive South American Tomato Pinworm Tuta absoluta

The South American tomato pinworm (Tuta absoluta) has recently invaded Europe and is rapidly spreading in the Afro-Eurasian continent where it is becoming a major pest on tomato crops. Laboratory tests were undertaken to evaluate the potential of 29 European strains of Trichogramma parasitoids to control T. absoluta. In addition to the host itself, the host plant (tomato) was used during the laboratory tests in order to increase the chance of selecting the best parasitoid strains. Trichogramma females were placed with T. absoluta eggs on a tomato leaflet in tubes. We compared the parasitism of T. absoluta by the various Trichogramma species tested to the Trichogramma species currently commercially available for the pest control in Europe, i.e. Trichogramma achaeae. Thereafter, the more promising strains were tested on a larger scale, in mesocosm (i.e. cages in greenhouses) and in greenhouse compartments to evaluate efficiency of laboratory selected strains under cropping conditions. The most efficient strain from the laboratory screening trials did not perform as efficiently under the greenhouse conditions. We discuss differences in parasitism levels among species and strains and among the different scales tested in the experiments, as well as implications of these results for further screening for biocontrol agents.