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Major advance in sleeping sickness drug made by Glasgow scientists

A new study published in the open-access journal PLoS Neglected Tropical Diseases on September 6th presents a key advance in developing a safer cure for sleeping sickness. Led by Professor Peter Kennedy, researchers at the University of Glasgow's Institute for Infection, Immunology and Inflammation have created a version of the drug most commonly used to treat sleeping sickness which can be administered orally in pill form.

Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease of major importance. Transmitted by the tsetse fly and caused by the trypanosome parasite, sleeping sickness is invariably fatal if left untreated. Once the disease has crossed the blood-brain barrier and entered the central nervous system the most commonly used treatment is an intravenous course of the arsenic-based drug melarsoprol. Because melarsoprol has a low solubility in water, it is dissolved in propylene glycol and administered intravenously. The result is a highly-toxic drug that kills five per cent of patients receiving it and leaves many others permanently brain-damaged.

Researchers at the University of Glasgow combined melarsoprol with cyclodextrins molecules that surrounded the drug allowing it to be administered orally, increasing its solubility and releasing the drug more slowly in the gut. In laboratory tests the altered drug was shown to retain its ability to kill the infection, and was able to cure mice infected with the parasite after a seven-day daily oral dosing schedule. The drug cleared parasites from the brain and restored normal blood-brain barrier integrity.

According to Prof. Kennedy, "This new research is the most clinically important in the 20 years of our trypanosome research group. It has the potential of a major therapeutic advance and if it is equally effective in humans then it would also have a significant socio-economic impact because the duration of inpatient treatment would be shorter and some patients might even be eventually treated at home."

Prof Kennedy added: "You always have to be very cautious when extrapolating results from mouse models to the human disease but there are several reasons why we are quietly optimistic that this may very well work in humans too.

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PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS NEGLECTED TROPICAL DISEASES (www.plosntds.org) AS THE SOURCE FOR THIS ARTICLE AND PROVIDE A LINK TO THE FREELY AVAILABLE TEXT. THANK YOU.

PLoS Neglected Tropical Diseases is an open-access, peer-reviewed journal published weekly by the Public Library of Science (PLoS).

EMBARGO in place until: Tuesday, September 6th, 2011, 2pm Pacific/5pm Eastern Time

FINANCIAL DISCLOSURE: This research was funded by the Medical Research Council (G0601059, http://www.mrc.ac.uk/index.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

COMPETING INTERESTS: The authors have declared that no competing interests exist.

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.pntd.0001308 (link will go live upon embargo lift)

CITATION: Rodgers J, Jones A, Gibaud S, Bradley B, McCabe C, et al. (2011) Melarsoprol Cyclodextrin Inclusion Complexes as Promising Oral Candidates for the Treatment of Human African Trypanosomiasis. PLoS Negl Trop Dis 5(9): e1308. doi:10.1371/journal.pntd.0001308

CONTACT: Stuart Forsyth or Ross Barker at the University of Glasgow Media Relations office, tel 0141 330 3535, email stuart.forsyth@glasgow.ac.uk / ross.barker@glasgow.ac.uk

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