Schistosome Study reveals Potential for Drug target Discovery

A study into the basic biology of parasitic flatworms known as schistosomes has revealed potential weaknesses in their biology which could lead to new treatments for a tropical disease estimated to kill up to 250,000 people every year.

Schistosomiasis, affecting mostly children in Africa, Asia and South America, leads to organ failure or parasite-induced cancer and can leave victims with long term symptoms of chronic infection.

The work(1) has been led by Dr James Collins III’s team at the University of Texas Southwestern (UTSW) with Dr Matthew Berriman’s group at the Wellcome Sanger Institute offering genome support and Professor Karl Hoffmann and Dr Gilda Padalino at Aberystwyth University providing key validation experiments.

The parasite that causes this disease has a complicated life cycle that involves stages in both freshwater snails and mammals. Currently only one drug, praziquantel, is available to treat this condition, although it doesn’t kill all intra-mammalian stages of the schistosome life cycle and it has a variable cure rate in some endemic settings.

Collins and his collaborators embarked on a molecular study to better understand these organisms, using functional genomics to characterise the role of about 20% of Schistosoma mansoni’s protein coding genes – 2,216 in total. Previously, only a handful of genes in these organisms had been assessed in this fashion.

As part of this study, Professor Hoffmann and Dr Padalino were responsible for confirming the functional genomics findings generated by their University of Texas Southwestern collaborators.

The Aberystwyth team, funded by the Wellcome Trust used a unique UK resource comprised of both the S. mansoni lifecycle and high-throughput drug discovery platforms to confirm the importance of key proteins involved in the parasite’s biology. This information is now being used to progress the discovery of new drugs to combat the disease.

Professor Hoffmann said: “For over 40 years, schistosomiasis has been predominantly controlled by a single drug, praziquantel. Without a vaccine on the horizon, we urgently need to find new drugs in case praziquantel resistance takes hold.  For the first time, using combinatorial methods for characterising both gene function and parasite responses at a scale not previously achievable, this study identifies several new starting points for rapidly accelerating our development of urgently-needed therapies. We are incredibly pleased to contribute to such an important public health initiative attempting to improve the lives of millions of people living in the most resource-poor communities on our planet.”