Biomed Briefs

SECRETS OF A CRITICAL SCHISTOSOMIASIS DRUG UNLOCKED

Staff Scientists Frédéric Chevalier, PhD, and Winka Le Clec’h, PhD, check on snails that are a vector for the parasites that cause schistosomiasis.

For decades, no one really knew how the drug praziquantel treated schistosomiasis, a parasitic worm infection afflicting more than 200 million people worldwide. Texas Biomed Professor Tim Anderson, PhD, and his team, and researchers at the Medical College of Wisconsin, determined how the drug works on the molecular level to kill the tiny flatworms.

The teams worked independently using different methods, and both came to the same conclusion, indicating the results are very robust. They found the drug binds to a channel in the worms’ cell membranes, leading to a flood of calcium ions entering the cells, causing paralysis and death. However, the drug is only about 70% effective.

The insights lay the groundwork for diagnostic tests to identify drug-resistant parasites and for developing new treatments. The five year project was published in Science Translational Medicine.


ZIKA VACCINE SHOWS PROMISING RESULTS IN PRECLINICAL STUDIES

Texas Biomed and its Southwest National Primate Research Center (SNPRC) played a critical role in testing how well a vaccine candidate prevented Zika virus from passing from mother to fetus in animal models. Zika causes miscarriages and severe developmental defects in human newborns, and is a World Health Organization public health emergency of international concern. The vaccine, developed at the Walter Reed Army Institute of Research, had been shown to elicit an immune response in adults, but testing on pregnant women is restricted for ethical and safety concerns. Collaborators at Trudeau Institute evaluated the vaccine in mice, while Texas Biomed researchers, led by Professor Jean Patterson, PhD, evaluated it in marmosets. The vaccine was 80% effective at preventing fetal malformations in mice and 90% effective at blocking the virus in marmoset offspring. The study was published in npj Vaccines.


MINIMIZING ERRATIC MOVEMENTS FOR PARKINSON’S PATIENTS

The small molecule PD13R (magenta) interacting with the dopamine D3 (grey) and D2 (purple) receptors, as predicted by SwRI’s drug discovery software, Rhodium™.

Uncontrolled muscle movements often emerge as a side effect of the primary medication used to treat Parkinson’s disease. Texas Biomed Associate Professor Marcel Daadi, PhD, and his collaborators have shown a compound, called PD13R, can reduce those movements by more than 85% in the marmoset model of Parkinson’s. The results were published in Experimental Neurology. Southwest Research Institute (SwRI)’s Rhodium drug discovery software helped identify potential compounds that only bind to specific dopamine receptors, which is one of the hardest parts of developing effective medications for Parkinson’s and its side effects. Temple University collaborators synthesized PD13R so it could be tested in cells and animal models at Texas Biomed. With additional safety and efficacy studies, Dr. Daadi is optimistic clinical trials can begin within two years.


DIVERSE DNA SIGNATURES LINKED TO HEART DISEASE

Risk for heart disease does not look the same on the genetic level for different population groups. An international research team, led by Texas Biomed’s Professor Shelley Cole, PhD, and collaborators at Columbia University, analyzed detailed genetic data from nearly 9,400 participants in four long-term studies following different populations: American Indians in the Strong Heart Study; African-American, Hispanic and white women; men and women in Massachusetts; and black and white men and women in four U.S. communities. The researchers looked for changes in DNA activity, called methylation, associated with development of heart disease. While 33 methylation points were shared across populations, the results were mixed. The same points were associated with higher risk of heart disease in some groups and lower risk in others. This lack of a universal pattern suggests the need to tailor early warning indicators. The study was published in JAMA Cardiology.

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