New treatment for tropical diseases
Three deadly tropical diseases could be treated using a new chemical developed by scientists. Prevalent in Latin America, Asia and Africa, the diseases affect 20 million people worldwide, claiming 50,000 lives each year.
Chagas disease, Leishmaniasis and sleeping sickness are all caused by a class of parasite called 'kinetoplastids'. The infections are transmitted by blood-sucking insects that regurgitate the parasites into their victim's bloodstream when they feed.
Leishmaniasis, spread by types of sandfly, causes skin lesions and in its fatal form progresses to attack the internal organs. Chagas disease can also lead to organ failure, while trypanosomiasis - known as 'sleeping sickness' - targets the brain, causing mental deterioration, coma and eventual death.
Despite the severity of the symptoms, few effective drugs are available.
"If you look at the current treatments, they are pretty bad," explains Dr Elmarie Myburgh from the Centre for Immunology and Infection at the University of York. "A lot of them are toxic, and a lot of the treatments are intravenous or intramuscular, so it requires the patient to be treated in hospital."
Underinvestment in drug discovery for these diseases has meant that previously they have received little research attention.
Now, in a collaboration funded by the Wellcome Trust, the Universities of Glasgow, York and Washington, together with industrial partner Novartis, set about developing new treatments for the diseases.
After testing 3 million different chemicals, the team discovered a compound that kills the parasites without harming mammalian cells. The compound is a form of drug called a 'protease inhibitor' that works by binding to a specific protein - known as the 'target' - that is common to all three types of parasite. This stops the parasite cells from functioning properly, killing them off. Since then, the scientists have been modifying the compound to make it safer for humans and more effective against the parasites.
"The hard bit is actually finding a target" says Elmarie. "Once you know what the target is, then you can start to play around with the compound and figure out what you need to change ... to give you the optimal characteristics."
Reported this week in the journal Nature, the optimised compound, named GNF6702, was found to successfully treat all three parasites in mice. Moreover, the team showed that GNF6702 is even able to clear the sleeping sickness parasite Trypanosoma brucei from inside the brain. The team confirmed this using parasites specially engineered to emit light, making them easy to spot in the brain.
"Very importantly, we can check if we have actually cleared the parasites in the brain," Elmarie explains. "One of the important things is that the compound is able to get into the brain and kill the parasites, without harming the patient."
The goal of the collaboration is to produce a class of drugs capable of treating the diseases far more effectively than is currently possible.
"The next step is to see if we can optimise the compound even further. There's a whole range of backup compounds that we are also testing, because you never know whether something will eventually go through the full process of clinical trials... I think the idea would be to try and get an oral formulation - that's what everyone is hoping for - that we can find something that will allow patients to be treated much more easily."