Wednesday, January 25, 2012

DNA screening improves sleeping sickness treatment

Sleeping sickness is a disease that still results in thousands of deaths in Africa each year. It is spread by a parasite that lives inside so-called Tsetse flies, and is transmitted in a similar way as malaria. It is lethal if it remains untreated, and any neurological damage caused by the parasite is irreversible. We have only five functional drugs to combat the disease, which' effect is hampered by adverse effects when given to patients. Because we do not quite understand how the drugs work, a research group from London set out to investigate them, and used a genetic screening system to uncover how the drugs interact to kill the parasite. In the long term, this ought to help us improve treatment for this frequently fatal disease.

The set of drugs disturb, or make use of natural processes in the parasite causing sleeping sickness. However, if certain genes or proteins that the drugs interact with are missing or modified, they may not work. The problem is, we do not know which genes, or their products, they interact with. It makes it difficult to modify drugs for greater efficacy, or to develop a new set. The British scientists used a wide range of molecules that block the activity of individual genes, and combined them with drug therapy to kill the parasite. If it remained alive, it means the blocked gene was necessary to let the medicine do its job.

After conducting their experiments, the researchers were left with 55 genes that appeared to be necessary for drug function. It tells us something about the biological mechanism underlying their efficacy. Because we now know the gene interactions, we can develop additional drugs based on the uncovered mechanism. Genetic analysis may also reveal why the parasite infecting a patient has become resistant, which tells us something about alternative options we can explore. All in all, this greatly aids to our understanding of why the treatment works.

Sleeping sickness refers to the phase of the disease in which the parasite causes neurological damage. One of the symptoms is disruption of the sleep-wake cycle, keeping patients slumbering throughout the day. However, because the parasite infects the central nervous system, it affects more parts of the body's functioning, which can eventually be fatal. Sleeping sickness is a lot less casual than it sounds. The neurological phase is preceded by a phase characterized by fever, accompanied by swollen lymph nodes and pain. It is actually the phase in which the body's immune system tries to fight off the infection.

Diseases being spread by mosquitoes carrying dangerous parasites have naturally been hard to combat. We need to find their weak spots in order to be able to launch an effective treatment strategy. We have seen some success for the treatment of malaria recently, which is the most fatal of the parasitic mosquito-born disease. Being able to treat sleeping sickness more efficiently is equally relevant, despite lesser casualties, because the parasites seem to be developing resistance against the drugs we have to fight them. In addition to the genetic analysis helping us improving treatment, it may also give rise to a future vaccine to prevent sleeping sickness.

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