The findings are the result of a two-year investigation by Xiaorong Lin, assistant professor of biology, and Matthew S. Sachs, professor of biology, involving sertraline hydrocholoride (ZOLOFT) and its effects on Cryptococcus neoformans, the major causative agent of fungal meningitis — specifically, cryptococcal meningitis, which claims more than half a million lives worldwide each year, according to a 2009 Center for Disease Control (CDC) report.
Their research, funded with grants from the American Heart Association (AHA), the Norman Hackerman Advanced Research Program, and the National Institutes of Health (NIH), is published in the June issue of the American Society of Microbiology journal Antimicrobial Agents and Chemotherapy. Their research team includes Ph.D. candidate Bing Zhai and postdoctoral fellows Cheng Wu and Linqi Wang.
"The point here is that if there is a drug that already exists, is known to be well-tolerated, and has alternative uses, that's a good thing," Sachs says. "The billion dollars it would take to bring a drug to the market — that's already done."
C. neoformans is a potentially dangerous fungal pathogen found in many soils throughout the world that may cause systemic infections, particularly involving the central nervous system. In most cases, the microscopic, airborne fungal cells of C. neoformans cause asymptomatic colonization in the lungs. However, Lin says the fungus is particularly aggressive in people with weakened immune systems and can spread to other parts of the body, such as the brain and spinal cord, resulting in cryptococcal meningitis — a condition that, in absence of treatment, is fatal.
Lin participated in a previous study to screen a collection of FDA-approved drugs in a John Hopkins Clinical Compound Library to determine if any contained fungicidal agents. Although sertraline was shown to only moderately inhibit the effects of common fungal strains like Aspergillus nidulans, a genus of common mold often found on spoiled food, and Candida, a genus of yeast often associated with mammals, sertraline was found to be particularly effective against C. neoformans.
A follow-up investigation of sertraline in a mouse model of systemic cryptococcosis revealed that it combats infection similar to fluconazole, an antifungal drug used commonly since the early 1990s. Moreover, a drug combination of sertraline and fluconazole was found to work more efficiently than either drug alone.
Lin says that even though the infection ultimately proved fatal in the mice study, sertraline as a cryptoccol treatment still holds promise. Because sertraline reduced the overall fungal burden within the mice and also possesses the desirable ability to cross the blood-brain barrier as an antidepressant, there is still hope it can be altered to serve as a viable treatment option.
"The problem for many current antifungal drugs is that many cannot go to the brain, and it's very difficult for a lot of compounds to reach the brain in the first place," Lin says. "So, you run into the problem of not killing all the fungus or having a very low level of fungus still exist. The fact is, this antidepressant can cross the blood-brain barrier and can get into the tissue at high concentrations."
It remains unclear exactly what dosage and concentration of sertraline is necessary to completely eliminate cryptococcosis, especially cryptococcal meningitis, but Lin and Sachs hope those answers will come to light with further testing.
"If this becomes useful, it could represent a truly significant increase in our ability to help people with brain cryptococcal infections," Sachs adds.
To read the Texas A&M team's paper, visit http://aac.asm.org/content/56/7/3758.abstract?etoc.
For more information about Lin's and Sachs' respective research programs, go to http://www.bio.tamu.edu/FACMENU/FACULTY/LinX.htm or http://www.bio.tamu.edu/FACMENU/FACULTY/SachsM.php.Contact:
Shana Hutchins | EurekAlert!
Warming ponds could accelerate climate change
21.02.2017 | University of Exeter
An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
21.02.2017 | Earth Sciences
21.02.2017 | Medical Engineering
21.02.2017 | Trade Fair News