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The University of Southampton
Biological Sciences

The fight against parasitic worms: understanding a new resistance-breaking anthelmintic drug

A 15 year collaboration between biological scientists at the University of Southampton and Bayer AnimalHealth has broken new ground in the battle against parasitic worms (nematodes). Researchers have demonstrated that a new class of compounds, the cyclooctadepsipeptides, paralyses them through a completely new mechanism.

This knowledge has underpinned the registration and marketing of three new veterinary medicines starting with the award winning Profender Spot-on for cats in 2005. They have improved veterinary care for dogs and cats around the world, and enabled a world-leading animal health company to develop a new range of valuable drugs. It may also help the development of drugs to tackle human diseases caused by parasitic worms.

Research challenge

In 1993, Fujisawa Pharmaceutical Co Ltd in Japan filed a patent for a new chemical class of anthelmintic (anti-worm) drugs called cyclooctadepsipeptides. They could act against many types of gastrointestinal nematodes, including parasitic worms that attack livestock and pets. One drug in particular, the cyclooctadepsipeptide called emodepside, was taken up by Bayer AnimalHealth for its potential as a veterinary product.

Biological scientists at the University of Southampton were approached by the global pharmaceutical company in 1999 to lead research into how cylooctadepsipeptide drugs work against parasitic worms. Bayer AnimalHealth made the contact because of Southampton’s international reputation in nematode neurobiology. The initial collaboration involved Professors Lindy Holden-Dye and Robert Walker with Professor Dr Achim Harder of Bayer AnimalHealth and later included Southampton colleagues, Professor Vincent O’Connor and Dr Neil Hopper.

Context

Parasitic nematode worms infect humans, livestock and pets. This is a global problem affecting human health, animal welfare and food production.

Human and animal infections can be treated with anthelmintic drugs, such as Ivermectin which was developed in the 1980s. However, over the last two decades, such drugs have been losing their effectiveness and alternatives are needed.

Our solution

In 2002, Professor Harder from Bayer AnimalHealth reported that emodepside was effective against parasitic worms which were resistant to all other anthelmintic drugs and it could form the basis of a powerful new drug.

Southampton researchers provided the pharmaceutical company with the findings of their work on the effects of emodepside on the microscopic worm C. elegans, which explained the molecular basis of its resistance-breaking properties. This research supported the licensing of the veterinary medicines Profender® tablets and Procox®, by the European Medicines Agency and US Food and Drug Association. These added to the earlier successful licensing of Profender® Spot-on.

Bayer AnimalHealth has confirmed that Southampton’s explanation of emodepside’s mode of action was critical in bringing all three drugs to market.

Our impact

Bayer AnimalHealth’s new veterinary medicines have improved veterinary care for dogs and cats. The Profender range for cats has been on the market since 2005, and was awarded best new veterinary product at the Animal Health Industry Excellence Awards 2006. The jury commented that “Profender® Spot-on has become one of the highest-selling products in the industry within a short period of time”. Procox for puppies was approved for sale in 27 EU countries in 2011.

The marketing of these medicines was directly supported by the Southampton research.

The discovery of a drug to counter parasitic worms has influenced international debate concerning the treatment of human infections. The World Health Organisation is interested in emodepside as a new route to controlling filarial tropical diseases such as river blindness which afflict one sixth of the world’s population.

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