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New drugs hope to fight neglected tropical diseases

New drugs hope to fight neglected tropical diseases

Posted on 8 August 2016

Scientists say they are a step closer to providing effective treatments for three “neglected” diseases after making a chemical which can kill the parasites that cause the illnesses.

Trypanosoma brucei. Credit: Elmarie Myburgh

Chagas disease, leishmaniasis and human African trypanosomiasis (also known as sleeping sickness) affect 20 million people worldwide and lead to more than 50,000 deaths annually.

The diseases are caused by infection from parasites which have some similar biology and genomic sequence, suggesting that all three diseases could be cured with a single class of drug.

The scientists were able to identify an enzyme common to all three parasites and develop a chemical that binds to the “target” and prevents it from functioning.

The research, which was led by scientists from the Genomics Institute of the Novartis Research Foundation (GNF), included collaboration with colleagues at the Novartis Institute for Tropical Diseases (NITD), University of York, University of Washington and the University of Glasgow.

As part of the research, three million compounds held in the Novartis chemical library were tested by a phenotypic screen against live parasites and the most active then modified over 3,000 times using synthetic chemistry before the most potent one was identified.
Professor Jeremy Mottram, Chair in Pathogen Biology at the Centre for Immunology and Infection at the University of York, said: “It’s a breakthrough in our understanding of the parasites that cause the three diseases, potentially allowing them to be cured.

“This early phase drug discovery project will now move towards toxicity testing prior to human trials.”

The lead authors, who performed a significant part of the research at the University of Glasgow with in vivo imaging technologist Ryan Ritchie, focused on human African trypanosomiasis, a disease which is found in sub-Saharan Africa and which is transmitted by the tsetse fly.

The disease gets its more common name from the disturbance of the sleep cycle caused by the parasites infecting the brain, causing victims to fall into a coma and die.

Finding a drug that can target the disease in the brain has always been a challenge for scientists, but the team from York say they have made a breakthrough using an animal model of the human disease.

The research is published in the journal Nature.

Dr Elmarie Myburgh, from the Department of Biology at York, added: “We were able to detect the parasite in the brain using an imaging system that detects the presence of genetically modified light-emitting parasites.

“We then tested the chemical developed by Novartis using our imaging method which showed that it can get into the brain and kill the parasites.

“That is a very important finding because the drugs that are really needed in Africa are those that kill the parasites in the brain of patients with sleeping sickness.”

Dr Myburgh added: “It is a great example of collaboration between industry and academic partners; by combining resources and expertise you can really make significant scientific progress.”

The team from York are now part of a Wellcome Trust-funded consortium looking at progressing new drug candidates for the treatment of human African Trypanosomiasis.

Further information:

There are approximately two million cases of leishmaniasis per year in 88 countries worldwide, of which 500,000 are of the potentially fatal form of the disease (visceral leishmaniasis). Although mainly found in developing countries, Leishmania parasites are also found in most countries bordering the Mediterranean, and visceral leishmaniasis is now often associated with HIV infection.
African trypanosomiasis, also known as sleeping sickness, is caused by species of Trypanosoma brucei and is fatal if left untreated. Symptoms include headache, anaemia, joint pains and swollen tissues, while later in infection, neurological and endocrine disorders occur. As the parasites invade the central nervous system, mental deterioration begins, leading to coma and death. Sleeping sickness claims >50,000 deaths per year with up to 0.5 million cases annually. African trypanosomiasis is closely related to a widespread infection of cattle known as N'gana, which restricts cattle rearing in many prime areas of Africa.
120 million people are at risk from Chagas disease (caused by the parasite Trypanosoma cruzi) with 0.3 million new cases per year. Parasite infection results in fever and swollen lymph glands in the initial acute phase, symptoms that may lead to may severe illness and death, especially in young children. More commonly, patients enter a symptomless phase (of several months or years) when the parasites invade most organs of the body, often causing heart, intestinal and oesophageal damage and progressive weakness. In 32 percent of those infected, fatal damage to the heart and digestive tract occurs during this chronic phase.
For more information please visit the Centre for Immunology and Infection and the Department of Biology.