Breakthrough in treatment of sleeping sickness

April 3, 2009,

(PhysOrg.com) -- Scientists at the University of Glasgow have made a significant breakthrough in the treatment of Sleeping Sickness, otherwise known as Human African Trypanosomasis.

The experts, from the university’s medical, veterinary and life sciences faculties, believe the discovery, published this week in 'Brain', a leading neurological science journal, could potentially lead to the development of safer drugs for sleeping sickness in the future.

Sleeping Sickness is widely recognised as one of Africa’s neglected diseases killing up to 50,000 people every year. It causes an infection of the that is always fatal if untreated. But current treatments are far from safe or effective. Melarsoprol, an arsenic based drug, is the most common treatment given for sleeping sickness. However, it is so toxic that it kills one in 20 patients who are given it. With most fatalities, patients die from a very severe triggered by Melarsoprol.

University of Glasgow researchers have now identified that by inhibiting a particular metabolic pathway in the brain, known as the kynurenine pathway, they can significantly reduce the inflammation found in the brains of animals infected with the or trypanosomes which cause sleeping sickness. It is inflammation in the brain which kills patients, rather than the parasite itself.

The study published in Brain was led by Peter Kennedy, Burton Professor of Neurology at the University of Glasgow, and builds on previous research carried out by study co-authors Professor Trevor Stone, Professor Mike Barrett and Dr Jean Rodgers.

Professor Kennedy explains: “The kynurenine pathway is a major metabolic pathway in humans active in many tissues including the brain. It can induce inflammation when stimulated. Pharmacologists have found that specific drugs aimed at the pathway can be useful in dampening down inflammation. Professor Stone and his research group showed a similar involvement of the kynurenine pathway in the fatal brain inflammation that occurs in cerebral malaria.

“It has been known for sometime that Melarsoprol is capable of killing patients by profoundly damaging their brains. Exactly how this happens remains unclear, but it seems likely that the drug kills the parasites very rapidly and profound inflammatory responses to those dying parasites cause damage to the brain cells in their vicinity. This can lead to death of the patients.”

Scientists now hope the new finding could mean drugs intended to dampen down inflammatory reactions within the brain could be given to patients to reduce the risk of the drug induced toxicity when treating sleeping sickness.

Professor Kennedy continues: "We are unquestionably one step closer to developing safer combination drugs for the treatment of sleeping sickness. Our study with mice showed that if you inhibit the kynurenine pathway with an anti-inflammatory drug or agent you minimise damage to the brain. This lessens the risk of death. Therefore, we believe that when treating patients with Melarsoprol it would be possible to minimise brain damage if a specific anti-inflammatory drug was administered before the patient received melarsoprol. We will of course need to test this theory, but this finding is extremely promising."

Sleeping Sickness occurs in 36 countries in sub-Saharan Africa and is a major health problem in Angola, the Democratic Republic of Congo, Uganda and Sudan. The trypanosome parasite is transmitted by the tsetse fly. If untreated, the trypanosome crosses the blood-brain barrier to invade the nervous system inducing confusion, paralysis, coma and a reversal of the normal the sleep cycle - where the disease gets its name.

Professor Kennedy is the author of 'The Fatal Sleep' published in 2007 by Luath Press.

More information: A copy of the paper is available at: brain.oxfordjournals.org/cgi/content/full/awp074
Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis, Brain, Advance Access published on March 31, 2009 doi:10.1093/brain/awp074.

Provided by University of Glasgow

Related Stories

Recommended for you

In a break with dogma, myelin boosts neuron growth in spinal cord injuries

May 23, 2018
Recovery after severe spinal cord injury is notoriously fraught, with permanent paralysis often the result. In recent years, researchers have increasingly turned to stem cell-based therapies as a potential method for repairing ...

Leg exercise is critical to brain and nervous system health

May 23, 2018
Groundbreaking research shows that neurological health depends as much on signals sent by the body's large, leg muscles to the brain as it does on directives from the brain to the muscles. Published today in Frontiers in ...

Memory molecule limits plasticity by calibrating calcium

May 23, 2018
The brain has an incredible capacity to support a lifetime of learning and memory. Each new experience fundamentally alters the connections between cells in the brain called synapses. To accommodate synaptic alterations, ...

New type of vertigo identified

May 23, 2018
Neurologists have identified a new type of vertigo with no known cause, according to a study published in the May 23, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology.

Study confirms that men and women tend to adopt different navigation strategies

May 23, 2018
When navigating in a known environment, men prefer to take shortcuts to reach their destination more quickly, while women tend to use routes they know. This is according to Alexander Boone of UC Santa Barbara in the US who ...

Changes to specific MicroRNA involved in development of Lou Gehrig's disease

May 23, 2018
A new Tel Aviv University study identifies a previously unknown mechanism involved in the development of Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS). The research focuses on a specific microRNA whose levels ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.