Breakthrough research at the University of Dundee may lead to treatments that make two deadly parasitic infections a thing of the past.
Experts at the University’s Drug Discovery Unit and Mode of Action group in the School of Life Sciences have contributed to the development of two drug compounds that have the potential to revolutionise treatment of Chagas Disease and visceral leishmaniasis, parasitic infections that kill thousands of people every year.
Other partners in this global effort include GSK, the Drugs for Neglected Diseases initiative (DNDi), the London School for Hygiene and Tropical Medicine, the University of Antwerp, Monash University, Epichem and Griffith University.
One of the compounds, named DNDI-6174, is highly effective in models of visceral leishmaniasis infection and has suitable properties for further clinical development. Meanwhile, combining a compound closely related to DNDI-6174 with lowered doses of the clinically used drug benznidazole was found to effectively cure Chagas disease in an experimental model, after only five days of treatment. Finding ways to reduce both the levels and treatment duration of benznidazole required to cure Chagas disease is deemed as highly advantageous, with the drug associated with severe side effects that often prevent patients from completing treatment regimens.
Dr Manu De Rycker, Head of Translational Parasitology within Dundee’s School of Life Sciences, said, “It is hard to understate the significance of these two breakthroughs."
“Both Chagas disease and visceral leishmaniasis claim thousands of lives every year, often in some of the most deprived regions of the world. Current treatment options are inadequate and there is an urgent need for new therapeutics. The research we are publishing presents exciting opportunities to develop potentially transformative treatments."
“Our Drug Discovery Unit and the Mode of Action group are leading the way in developing potential new treatments for Neglected Tropical Diseases, but this is incredibly complex work."
"These success stories are testament to the commitment of our researchers and the collaborative work we conduct with our partners.”
Dr Susan Wyllie, Head of the Mode of Action group, said
“I am delighted that my group were able to make significant contributions to both studies."
"The primary goal of the Mode of Action group is to facilitate the development of new drugs to treat the world’s most neglected diseases."
"It is fantastic that these highly collaborative studies represent a step closer to making these new treatments a reality.”
Visceral leishmaniasis is transmitted by infected sandflies that bite humans. Infection causes fever, weight loss and anaemia and if left untreated is fatal in more than 95% of cases. Over 50,000 new cases occur annually, often associated with malnutrition, weak immune systems, poor housing, and lack of resources. Approximately 600 million people are at risk of visceral leishmaniasis, mainly in East Africa, India, and Brazil.
The World Health Organisation estimates that between six and seven million people around the world are infected with Trypanosoma cruzi, the parasite that causes Chagas disease.
Once found solely within Central and South America, it is spread by Triatomine bugs, which typically live in the walls or roofs of poorly constructed homes. They awake at night, biting exposed areas of skin and defecating nearby. The infection is spread when the person unwittingly smears infected faeces into damaged skin, their eyes or mouth. It can subsequently be spread by blood transfusion and from mother to child.
Patients often do not know they are infected, and the parasite can live inside a person’s body for years before killing its host. Current treatments are both limited in effectiveness and cause significant side-effects.
“The development of these compounds has been a fully collaborative effort, driven by the urgent need for simplified, short-course, oral treatments for people affected by visceral leishmaniasis and Chagas disease,” said Stéphanie Braillard, Nonclinical Development Leader at the DNDi.
“The University of Dundee is an important partner in the work to develop safe, effective, and affordable treatments for neglected populations.”
