Nav: Home

Discovery of enzyme in the sleeping sickness parasite streamlines drug development

April 18, 2016

Researchers from Umeå University in Sweden have discovered that the single-celled parasite causing African sleeping sickness has a defence mechanism against potential pharmaceuticals under development against the disease. The deadly parasite has an enzyme that can cleave and hence disarm adenosine analogue pharmaceuticals. This according to a study recently published in the Journal of Biological Chemistry.

African sleeping sickness is caused by the single-cell parasite Trypanosoma brucei and is spread by infected tsetse flies in sub-Saharan Africa. The disease is deadly, affecting both humans and livestock. At present, no vaccine exists and the pharmaceuticals available are highly toxic, troublesome to use or can only be used on some variants or stages of the disease. The only medication that can treat all forms of the disease in humans is Melarsoprol, which in 5-10 percent of treatments leads to fatal brain damages.

The disease can erupt epidemics and the number of sleeping sickness cases in the last 20 years has varied between 20,000 and 500,000. In the last decade, the number of cases has been limited for instance thanks to discovering patients and treating them before they carry the disease on. But researchers have warned that an increased resistance against antibiotics among parasites can lead to an intensification in the number of cases again. This is why there is a great need of new pharmaceuticals. In animal models, researchers have seen promising results with so-called adenosine analogues, a drug group usually used on other diseases but yet not on African sleeping sickness.

To survive, this parasite is fully dependent on purines - nutrients absorbed from the blood and used as building blocks to produce RNA and DNA. This dependency is something is exploited in the development of pharmaceuticals. The idea is to develop adenosine analogues that are similar to natural purines and are therefore absorbed by the parasites, but subsequently damage them. These substances can be used to cure mice infected with the disease but have so far not been tested on human sleeping sickness patients.

"Up until now, researchers have been unaware of why some pharmaceuticals based on adenosine analogues work against sleeping sickness whereas others don't," says Anders Hofer, researcher at the Department of Medical Biochemistry and Biophysics and last author of the article in the Journal of Biological Chemistry. "We are now able to show that the parasite has an enzyme able to cleave some of the adenosine analogues and this gives us an idea of why some drugs don't work."

The discovery enables researchers to control if the adenosine analogues that previously only had low efficiency on the parasite are cleaved by this enzyme. The pharmaceutical substances able to be cleaved by the parasite could then be made more efficient by changing their molecular construction in order for them not to be recognised by the enzyme.

"By manipulating the chemical structures of the more inefficient drugs, we are hoping to render them uncleavable and in that way bypass the parasite's protective enzyme. In doing so, it would be possible to develop many more pharmaceutical candidates to choose from, which would increase the opportunities to find a final drug with as few and harmless side effects as possible for use on humans," says Anders Hofer.
Researchers behind the study are or have been active at the Department of Medical Biochemistry and Biophysics at Umeå University (Munender Vodnala, Farahnaz Ranjbarian, Anna Pavlova and Anders Hofer) and at the University of Glasgow in Scotland (Harry P. de Koning).

Umea University

Related Sleeping Sickness Articles:

Severe morning sickness associated with higher risk of autism
Children whose mothers had hyperemesis gravidarum -- a severe form of a morning sickness -- during pregnancy were 53% more likely to be diagnosed with autism spectrum disorder, according to Kaiser Permanente research published in the American Journal of Perinatology.
Scientists identify a key gene in the transmission of deadly African sleeping sickness
An international team of life scientists has identified a key gene in the transmission of African sleeping sickness -- a severe disease transmitted by the bite of an infected, blood-sucking tsetse fly, which is common in Sub-Saharan Africa.
Marijuana for morning sickness? It's not great for baby's brain
With a growing number of states legalizing recreational or medical marijuana, more women are using the drug during pregnancy, in part due to its reported ability to relieve morning sickness.
New therapeutic approach to combat African sleeping sickness
Scientists working in a range of disciplines joined forces to identify a new approach to combat African sleeping sickness.
Sleeping sickness parasite uses multiple metabolic pathways
Parasitic protozoa called trypanosomes synthesize sugars using an unexpected metabolic pathway called gluconeogenesis, according to a study published December 27 in the open-access journal PLOS Pathogens by David Horn of the University of Dundee in the UK, and colleagues.
Decoding sleeping sickness signals could aid quest for treatments
Scientists have discovered how the parasite that causes sleeping sickness initiates a physical change in order to spread the disease.
Clemson researchers reveal secrets of parasite that causes African sleeping sickness
A team of Clemson University researchers wants to protect humans and other mammals from the debilitating and even deadly effects of African sleeping sickness.
Motion sickness vs. cybersickness: Two different problems or the same condition?
Contrary to previous research, severe motion sickness and cybersickness -- a type of motion sickness that stems from exposure to virtual reality -- may be considered the same clinical condition, according to researchers.
Virtual reality motion sickness may be predicted and counteracted
Researchers at the University of Waterloo have made progress towards predicting who is likely to feel sick from virtual reality technology.
Sleeping sickness: Pathogens camouflage themselves with sugar
It has long been known that the pathogens causing sleeping sickness evade the immune system by exchanging their surface proteins.
More Sleeping Sickness News and Sleeping Sickness Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab