Derivatives from oxamniquine show efficacy in fight against the disease schistosomiasis
San Antonio, Texas (November 24, 2020) – Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), The University of Texas San Antonio (UTSA) and Texas Biomedical Research Center (Texas Biomed) re-engineered the drug compound oxamniquine (OXA), paving the way for potential new treatments to prevent drug resistance among people infected with schistosomiasis, a parasitic disease that impacts 240 million people worldwide, according to the World Health Organization (WHO). Results from the study were recently published in the journal PLOS Neglected Tropical Diseases.
The WHO reports that schistosomiasis kills approximately 200,000 people annually and infects over 200 million people. Chronic schistosomiasis can lead to complications of the liver, bladder cancer and death. Schistosomiasis is primarily treated by the drug praziquantel (PZQ). Due to the drug’s moderate effectiveness and concern about drug-resistance, researchers are exploring strategies to develop additional treatments. Drug resistance is caused when a microbe that causes disease – in this case, a parasitic worm – gains mutations and no longer respond to treatment.
Professor Phil LoVerde, Ph.D. and Associate Professor Stanton McHardy, Ph.D., both with the Center for Innovative Drug Discovery, were the principal investigators on this collaborative study. Texas Biomed Professor Tim Anderson, Ph.D. contributed to the study along with a team of researchers from Texas Biomed, UT Health San Antonio and UTSA.
The researchers designed and synthesized derivatives, or drug compounds similar to OXA from the original formulation of OXA. These derivatives eliminated all three schistosomiasis species in vitro. The three species of flatworms that cause schistosomiasis are: S. mansoni, S. haematobium, and S. japonicum. Praziquantel is moderately effective against all three species; however, its predecessor, oxamniquine, is only effective against adult S. mansoni. Structural data from another UT Health San Antonio and Texas Biomed collaborative study using crystallographic analyses, an x-ray of a drug’s crystallized form, assisted the team in identifying points that could be restructured to allow oxamniquine to act differently once it is in the body.
“Coming into this study, we knew oxamniquine was effective against adult S. mansoni, and we know how the drug works,” Dr. LoVerde said. “We wanted to make some small tweaks to it to make it work a little better. Our team identified and tested multiple derivatives and conducted tests in vitro, resulting in the development of potential new drugs to treat all three species.”
Researchers plan to test the derivatives in an animal model to fully determine its efficacy and establish a potential combination drug therapy that would eliminate drug-resistance in the parasites.
“Texas Biomed has collaborated with other San Antonio researchers on schistosomiasis drug resistance for more than 10 years,” Dr. Anderson said. “We don’t exactly know how prevalent drug resistance is in schistosomes, but we do know it can occur and spread. Texas Biomed played a role in precursor studies, the establishment and design of this study and provided analysis of data.”
Other team members who contributed to this study are UT Health San Antonio scientists Meghan A. Guzman, Ph.D., Anastasia R. Rugel, Ph.D., Sevan N. Alwan, Ph.D., Stephen P. Holloway, Ph.D., Xiaohang Cao, M.D., Reid S. Tarpley, Alexander B. Taylor and Dmytro P. Kovalskyy, along with Frédéric D. Chevalier, Ph.D. at Texas Biomed.
Funding for collaborative work on schistosomiasis at Texas Biomed, UT Health San Antonio and UTSA comes from National Institutes of Allergies and Infectious Diseases, and from the Bill & Melinda Gates Foundation.
The University of Texas Health Science Center at San Antonio, also referred to as UT Health San Antonio, is one of the country’s leading health sciences universities and is designated as a Hispanic-Serving Institution by the U.S. Department of Education. With missions of teaching, research, patient care and community engagement, its schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have graduated more than 37,000 alumni who are leading change, advancing their fields, and renewing hope for patients and their families throughout South Texas and the world. To learn about the many ways “We make lives better®,” visit www.uthscsa.edu.
The University of Texas at San Antonio (UTSA) is a Hispanic Serving University specializing in cyber, health, fundamental futures, and social-economic development. With more than 32,000 students, it is the largest university in the San Antonio metropolitan region. UTSA advances knowledge through research and discovery, teaching and learning, community engagement and public service. The university embraces multicultural traditions and serves as a center for intellectual and creative resources as well as a catalyst for socioeconomic development and the commercialization of intellectual property—for Texas, the nation and the world. Learn more online, on UTSA Today or on Twitter, Instagram, Facebook, YouTube or LinkedIn.
Texas Biomed is one of the world’s leading independent biomedical research institutions dedicated to eradicating infection and advancing health worldwide through innovative biomedical research. Texas Biomed partners with researchers and institutions around the world to develop vaccines and therapeutics against viral pathogens causing AIDS, hepatitis, hemorrhagic fever, tuberculosis and parasitic diseases responsible for malaria and schistosomiasis disease. The Institute has programs in host-pathogen interaction, disease intervention and prevention and population health to understand the links between infectious diseases and other diseases such as aging, cardiovascular disease, diabetes and obesity. For more information on Texas Biomed, go to www.TxBiomed.org.