The Texas Biomedical Research Institute has received $2 million to identify new ways of determining treatment efficacy in Chagas disease, a potentially fatal tropical disease that affects nearly eight million people throughout the world and hundreds of thousands in the United States.
The organization Drugs for Neglected Diseases initiative (DNDi) received an award of $3 million from the Wellcome Trust, about $2 million of which will go to Texas Biomed as a sub-contractor. John L. VandeBerg, Ph.D., Texas Biomed’s chief scientific officer, is the organization’s principal investigator on the project. The announcement was made today at the 61st Annual Meeting of the American Society of Tropical Medicine and Hygiene in Atlanta.
Chagas disease is the leading parasitic killer in the Americas, where it causes more deaths than malaria. In the United States, the Centers for Disease Control and Prevention estimates that 300,000 or more are infected. Moreover, health officials say that in South Texas they have identified increased numbers of ‘kissing bugs’ that carry the parasite that causes the disease.
No easy-to-use and reliable test available can now assess if Chagas patients are rid of the parasite after treatment. Current treatment options have significant limitations due to safety considerations, inconsistent efficacy, and long treatment duration. Determining if treatment has cured the infection requires difficult and lengthy repeat laboratory testing that can sometimes take decades due to the unusual chronic nature of the disease.
Patients and physicians are often skeptical of the benefit of treatment for the chronic, indeterminate form of Chagas without a direct way to measure cure. A new, robust test for the disease burden would help to expand treatment, as well as provide a valuable tool for accelerating the evaluation of new drugs in clinical trials.
The $3 million Wellcome Trust Award will fund the first-ever large-scale study involving treatment of non-human primates (macaques) naturally infected in their outdoor living environment with the parasite that causes Chagas disease, Trypanosoma cruzi. The animals will be treated with three drug regimens versus placebo: benznidazole at optimal dose, benznidazole at suboptimal dose, and another azole compound with anti-parasite activity. Over a period of 12 months after treatment, the animals will be examined for clearance of the Chagas parasite through polymerase chain reaction (PCR) and other tests. The primary goal of the study is to see if these tests can accurately measure parasitological cure.
"We established the monkey model for research on Chagas disease because progress has been extremely slow in developing candidate treatments for it, and even slower in developing ways to assess the efficacy of candidate treatments,” said VandeBerg. “The research supported by this grant will greatly enhance our capacity to assess the efficacy of existing candidate treatments for Chagas disease, as well as those that will be developed in the future."
“We need to be able to tell patients whether or not their treatment has worked,” said Graeme Bilbe, Ph.D., Research and Development Director for DNDi. “The results of this study could encourage treating more patients now, with what we have, and facilitate future clinical trials of new treatments for chronic Chagas disease patients.”
The project was initiated by VandeBerg and Rick Tarleton, Ph.D., of the Center for Tropical and Emerging Global Diseases at the University of Georgia. The study will be coordinated by DNDi with these partners and will begin within months and run until 2015. Texas Biomed will conduct the experimental protocols with the animals and will conduct biomarker analysis, along with the University of Georgia. Other partners conducting testing will be the University of Texas at El Paso, the genomic services company Gentris, and the Argentinean National Council of Scientific and Technical Investigation. To facilitate future biomarker discovery efforts, the biological samples collected in the study will be stored at Texas Biomed and made available to other researchers.
About Chagas disease
Chagas disease is endemic in 21 countries across Latin America, where it kills more people than any other parasite-borne disease, including malaria. It currently infects approximately 8 million people, kills an estimated 12,000 per year, and places 100 million people at risk. Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. In 30-40 percent of cases, chronic Chagas disease affects the heart and/or the digestive system. It is potentially fatal and the leading cause of heart failure in Latin America, resulting in frequent and prolonged hospitalization, use of pacemakers and defibrillators, and heart transplants. The disease causes loss of productivity among tens of thousands of young, working-age adults across Latin America, with over a billion dollars in estimated economic losses annually. As a result of worldwide population flow, Chagas disease is no longer confined to Latin America, with patient numbers growing in the United States, Europe, Australia, and Japan.
The Drugs for Neglected Diseases initiative (DNDi) is a not-for-profit research and development organization working to deliver new treatments for neglected diseases, in particular sleeping sickness (human African trypanosomiasis), Chagas disease, leishmaniasis, specific helminth infections, malaria, and pediatric HIV. DNDi was established in 2003 by Médecins Sans Frontières/Doctors Without Borders, the Oswaldo Cruz Foundation of Brazil, the Indian Council of Medical Research, the Kenya Medical Research Institute, the Ministry of Health of Malaysia, and the Pasteur Institute of France. The Special Programme for Tropical Disease Research serves as permanent observer. DNDi currently has one lead drug candidate, E1224 (ravuconazole pro-drug), in clinical development for the treatment of Chagas disease, and two other drug classes in preclinical development.
Since its inception in 2003, DNDi has delivered six new treatments for neglected patients: two fixed-dose antimalarials (ASAQ and ASMQ), nifurtimox-eflornithine combination therapy (NECT) for late-stage sleeping sickness, sodium stibogluconate and paromomycin (SSG&PM) combination therapy for visceral leishmaniasis in Africa, a set of combination therapies for visceral leishmaniasis in Asia, and a pediatric dosage form of benznidazole for Chagas disease.
DNDi has helped establish three clinical research platforms: Leishmaniasis East Africa Platform in Kenya, Ethiopia, Sudan, and Uganda; the HAT Platform based in the Democratic Republic of Congo for sleeping sickness; and the Chagas Clinical Research Platform in Latin America. Strong regional networks such as these help strengthen research and treatment-implementation capacity in neglected disease-endemic countries. www.dndi.org
About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
About Texas Biomed
Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world's leading independent biomedical research institutions dedicated to advancing global human health through innovative biomedical research. Located on a 200-acre campus on the northwest side of San Antonio, Texas Biomed partners with hundreds of researchers and institutions around the world, targeting advances in the fight against AIDS, hepatitis, malaria, parasitic infections and a host of other infectious diseases, as well as cardiovascular disease, diabetes, obesity, cancer, psychiatric disorders, and problems of pregnancy. For more information on Texas Biomed, go to www.TxBiomed.org, or call Joe Carey, Texas Biomed’s Vice President for Public Affairs, at 210-258-9437.