Compound Might Defeat African Sleeping Sickness
- Date:
- August 27, 2005
- Source:
- University of North Carolina at Chapel Hill
- Summary:
- One of the most devastating diseases in sub-Saharan Africa almost disappeared in the late 1950s. That disease, African sleeping sickness, or trypanosomiasis, largely succumbed to heroic public health efforts -- including relocating entire villages. But in the past several decades, because of post-colonial turmoil, the catastrophic illness has come back to ravage parts of Angola, the Democratic Republic of the Congo, the Sudan and other countries. In some regions, the tsetse fly-borne infection rivals or exceeds the toll AIDS takes.
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CHAPEL HILL - One of the most devastating diseases insub-Saharan Africa almost disappeared in the late 1950s. That disease,African sleeping sickness, or trypanosomiasis, largely succumbed toheroic public health efforts -- including relocating entire villages.But in the past several decades, because of post-colonial turmoil, thecatastrophic illness has come back to ravage parts of Angola, theDemocratic Republic of the Congo, the Sudan and other countries. Insome regions, the tsetse fly-borne infection rivals or exceeds the tollAIDS takes.
Trypanosomiasis is passed from human to human bytsetse fly bites. It produces fever, lymph nodes inflammation, eventualimpairment of the brain and nervous system in its late stage and, ifnot treated, death. The World Health Organization has estimated thatmore then 300,000 people are infected, and more than 60 million livingin the region are at risk.
Now, real hope for a better treatmentis on the horizon, based on research conducted in part at theUniversity of North Carolina at Chapel Hill. In Phase II clinicaltrials, a new oral drug, DB289, demonstrated safety and higheffectiveness in subjects with the early stage of sleeping sickness.Scientists are launching a Phase III trial this summer involving forthe first time hundreds of patients who will be treated with the drug.
TheBill & Melinda Gates Foundation is supporting the work, which isbeing led by Dr. Richard R. Tidwell, professor of pathology andlaboratory medicine at the UNC School of Medicine.
"This is veryexciting time for us and the international consortium we pulledtogether to develop the first drug made to specifically combat thisterrible re-emerging disease," Tidwell said. "The compound DB289 willbe the first new drug for early stage (blood stage) African sleepingsickness in 50 years, and the only oral drug that's ever beenspecifically developed for it."
Oral administration is importantfor treating the disease which occurs in villages where it candevastate afflicted populations, he said. Small villages do not haveaccess to clinics or trained staff that can give injections oradminister drugs intravenously.
"Immtech International, Inc. ofVernon Hills, Ill., a pharmaceutical company and a contributor to thisdrug development effort, has an exclusive, worldwide license to DB289and related compounds developed by the UNC-based scientific consortiumfor African sleeping sickness and other devastating diseases such asTB, which together affect millions of people annually," Tidwell said."Besides DB289, several potential drug candidates in early developmentappear to be promising for treating late stage African sleepingsickness, which occurs when the parasite over time enters the brain."
Thenew drug candidates are active because they can cross the blood-brainbarrier, a biological wall that protects the nervous system naturallybut can block beneficial drugs, he said. Work is also progressingrapidly on a new drug for drug-resistant malaria, another major threatin developing countries.
The UNC-led Consortium to Develop NewDrugs for Protozoan Diseases established an advisory board chaired byDr. Frederick Sparling at UNC, with Drs. Terry Shapiro at Johns HopkinsUniversity, Ann Moore at the Centers for Disease Control and Preventionand Thomas Brewer at the Bill & Melinda Gates Foundation as boardmembers. Laboratories involved in the discovery of the new drugcandidates are run by internationally known scientists including Drs.David Boykin and David Wilson at Georgia State University, MichaelBarrett at the University of Glasgow, Raymond Mdachi at KenyaTrypanosomiasis Research Institute and Steven Meshnick and J. Ed Hallof UNC. Scientists also closely involved are Drs. Simon Croft at theLondon School of Hygiene and Tropical Medicine and Reto Brun andChristian Burri at the Swiss Tropical Institute.
"New drugs forillnesses in developing countries often fly beneath the profit radar oflarge pharmaceutical companies," Tidwell said. "That's because largecompanies require a high return on their investments, which means theydon’t have sufficient incentives to develop low-cost drugs. Despitebeing one of Africa's most prevalent and economically devastatingillnesses, sleeping sickness is definitely one of those that has beenneglected. For that reason, we decided to put this consortium together,and that's why the Bill & Melinda Gates Foundation was veryinterested in supporting our work."
The group has since becomeone of the models for public-private partnerships to discover anddevelop drugs for poorer countries or neglected diseases, Tidwell said.
"Wehave been able to reduce the cost of drug discovery to a fraction ofthe cost it would take a large drug company to do it, but we're notcutting corners, and we're using some of the best technology andscientists in the world to accomplish these goals," he said.
Dr.Carol Olson, vice president and chief medical officer of Immtech, saidshe and colleagues started the Phase III clinical trial this month. Thenew pivotal trial will involve approximately 250 patients in theDemocratic Republic of the Congo and the Sudan. Angola will be includedif a recent outbreak there of the Ebola-like Marburg virus remainsunder control.
"The Swiss Tropical Institute will be responsiblefor selecting patients and carefully monitoring the trials," saidOlson, who helped design and will oversee the study. She is aninfectious disease expert who retired after a long career with AbbottLaboratories.
"We're trying to improve the lives of thesepatients by treating the disease early on in the local villages beforeit progresses to the terminal brain stage," the physician said. "When adrug works and helps a lot of people, that's when all our hard workreally pays off, and we can be proud of our efforts."
Three yearsago, the National Foundation for Infectious Diseases presented itsJimmy and Roselyn Carter Humanitarian Award to Bill and Melinda Gates.That day, a talk by former President Jimmy Carter about the workRoselyn and he did in Africa inspired Olson to work on deadly butneglected illnesses, she said.
"What goes 'round, comes 'round,"Olson said. "We have a real opportunity with DB289 and other drugcandidates in the pipeline to help solve some very difficult healthproblems affecting millions of people in developing countries."
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Materials provided by University of North Carolina at Chapel Hill. Note: Content may be edited for style and length.
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