Five academic institutions, two governmental institutes and two leading Small – Medium Enterprises (SMEs) from Europe, Africa and Latin America are joining forces to develop novel drugs against parasites.

The 4-year EU-funded project led by VU University Amsterdam is called PDE4NPD: PhosphoDiEsterase inhibitors for Neglected Parasitic Diseases.

Neglected parasitic diseases (NPDs) form an enormous obstacle to the development of communities across the world. The diseases are classified ‘neglected’ as investments in finding cures for these illnesses are extremely low, especially when considering their devastating impact on human and veterinary health.

The NPDs addressed in this project – Chagas’ disease, human African trypanosomiasis, leishmaniasis and schistosomiasis – collectively result in 6.6 million disability-adjusted life years (DALYs).

During the last 30 years, only nine new drugs targeting these NPDs have come to market. Some of these treatments cause severe side effects, while others are very expensive or have severe toxicity issues.

A cause for this standstill is the lack of sufficient financial incentives and low return on investment for the pharmaceutical industry, but with resistance threatening the few treatments available, some NPDs are at risk of becoming untreatable and spreading to hitherto unaffected areas. Therefore, a paradigm shift in policy and a substantial joint effort to address this gap is urgently required.

The PDE4NPD project enables public and private partners to join forces within the EU Seventh Framework program to tackle these urgent healthcare needs. 

The consortium consists of VU University Amsterdam (NL), University of Glasgow (UK), University of Kent (UK), University of Antwerp (BE), The Spanish National Research Council (ES), Fundacao Oswaldo Cruz (BR), Theodor Bilharz Research Institute (EG), European Screening Port (DE), IOTA Pharmaceuticals (UK) and Top Institute Pharma (NL) and combines various drug discovery approaches into one platform that is dedicated to developing drugs against parasite PDEs, a family of well¬-characterized enzymes.

“Previous studies have shown that targeting PDEs, which are highly druggable, is a viable strategy to combat parasite diseases”, said principal investigator Rob Leurs of VU University, just like well-known drugs including Viagra and Daxas effectively target human PDEs.

“This consortium has all the expertise to develop parasite‐specific PDE inhibitors with high clinical potential. We have access to state-of-the-art structural biology and screening technologies for finding new molecules with drug-like properties.”

In parallel, parasitology research groups will perform phenotypic screening on various parasite species to identify agents that will kill them. From these screening paradigms, the consortium will develop compounds that demonstrate both anti-parasitic activity and inhibit PDEs as their cellular target.

Leurs said: “Ultimately, PDE4NPD will develop into a generic platform in which any parasite PDE can be enrolled. The integrative approach allows the accumulation of fundamental knowledge with an efficiency that is typical of approaches that focus on a single cellular target.”

Dr. Harry de Koning of the College of Medical, Veterinary and Life Sciences at the University of Glsagow, was principal investigator of the study that first proved that pharmacological inhibition of parasite PDEs is a viable therapeutic strategy, published as recently as 2012.

In this new consortium, his team will coordinate the efforts of the various parasitology groups that are testing the new compounds produced by the medicinal chemistry laboratories and liaise with the other partners on optimization strategies.

In addition, the De Koning group will be responsible for validating PDEs from various parasites as pharmacological drug targets.

Dr De Koning said: “This consortium encompasses partners with highly complementary skills and technologies for drug discovery and constitutes a tremendous opportunity to realize the potential of PDE inhibitors for the treatment of NPDs".

Further support for the development of PDE inhibitors as anti-parasitic agents comes through a partnership with Glaxo-Smith-Kline’s Open Lab Foundation and other collaborators from the USA.

 

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Media enquiries: stuart.forsyth@glasgow.ac.uk / 0141 330 4831

First published: 2 April 2014