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Arthritis Drug Powerful Against Human Dysentery

May 22, 2012
Image Caption: This micrograph stained with chlorazol black, revealed an Entamoeba histolytica cyst. Several protozoan species in the genus Entamoeba infect humans, but not all of them are associated with disease. Entamoeba histolytica is well recognized as a pathogenic ameba, associated with intestinal and extraintestinal infections. Credit: CDC/Dr. George Healy

Connie K. Ho for RedOrbit.com

Every year, 50 million people throughout the world contract amebiasis through contaminated food or water. With this shocking statistic, it is considered the third leading cause of illness and the fourth leading cause of death due to protozoan infection on a global basis.

A collaborative project by researchers from the University of California, San Francisco (UCSF), the University of California, San Diego (UCSD), and Wake Forest Medical School recently announced that they had found that an approved arthritis drug worked against these amoebas during lab and animal studies. This is a breakthrough in research, as the drug could be used to treat human dysentery that is caused by amoebic infections. The drug would be prepared in small, inexpensive doses and could be used by those in the developing world.

In developing countries, 70,000 deaths are reportedly caused by amebiasis and children are known to have the highest risk of contracting the disease. Noted effects of the parasite Giardia include diarrhea, abdominal cramps, and dehydration. Presently, amebiasis and giardiasis are treated with the antibiotic metronidazole, but it has side effects like dizziness, headaches, nausea, and vomiting.

Based on the experiment, researchers were able to get the drug auranofin approved under Orphan Drug Status from the U.S. Food and Drug Administration (FDA). It is slated to be tested in clinical trials with humans with regards to amebiasis and the parasite Giardia.

During the lab tests, auranofin demonstrated the ability to stop the growth of the parasite Entamoeba histolytica. The findings, published in the June 2012 issue of Nature Medicine, showed that existing drugs could have other uses and assist in treatment of other illnesses. According to co-senior author Dr. James McKerrow, the off-patent drug and the clinical safety data shows that there is the possibility for a low-cost solution that can be used globally; it will have fewer side effects and risks to bacterial infection than other therapy options that are currently offered.

“When we’re looking for new treatments for the developing world, we start with drugs that have already been approved,” explained McKerrow, a professor of pathology in the UCSF Sandler Center for Drug Discovery, in a statement. “If we can find an approved drug that happens to kill these organisms, we’ve leapfrogged the development process that goes into assessing whether they are safe, which also makes them affordable throughout the world.”

In the past, auranofin has been used by adults with rheumatoid arthritis and, since 1985, has been taken by patients orally twice-daily. The researchers believe that auranofin would be ten times stronger than the current treatments for dysentery. The drug could be given at low dose, once or a limited number of times.

“This is a drug that you can find in every country,” commented Dr. Anjan Debnath, lead researcher on the paper and a postdoctoral fellow at UCSF, in the statement. “Based on the dosage we’re seeing in the lab, this treatment could be sold at about $2.50 per dose, or lower. That cost savings could make a big difference to the people who need it the most.”

The project was an international collaboration between the California Institute for Quantitative Biosciences (QB3) at UCSF, the pathology departments at UCSD, and offices from the Instituto Politecnico Nacional in Mexico. Researchers at UCSF examined how to create a screen that could identify small molecule drugs that could safely eliminate amoebas. Debnath, who was a UCSD researcher at the time, developed a high-throughput screen that could work in an oxygen-free environment that was similar to the amoeba´s natural environment. The team also received a screening library of 900 compounds from Iconix Biosciences and worked with the Small Molecule Discovery Center to screen drugs against amoebas.

“The top hit was this drug auranofin, which caught our attention for a couple of reasons,” noted McKerrow in the statement. “First, it was more effective than the current drug, and importantly, it was a drug that has been given to people since 1985. So we knew it could be taken orally and was safer than the current drug for amoebas.”

In subsequent tests by UCSD and the Instituto Politecnico Nacional in Mexico, researchers found that the drug was effective, decreasing the number of parasites and lowering damage from inflammation. According to AFP, auranofin targeted the enzyme that shielded the parasite from oxygen; the parasite is particularly sensitive to oxygen. In terms of the FDA´s approval of auranofin for Orphan Drug Status, this will fast-track the drug. Orphan drugs status is given to those medicines that show promise in treating a disease that affects fewer than 200,000 persons in the U.S.

“This new use of an old drug represents a promising therapy for a major health threat, and highlights how research funded by the National Institutes of Health can benefit people around the world,” remarked Dr. Sharon L. Reed, a professor in the UCSD Departments of Pathology and Medicine, in a prepared statement.


Source: Connie K. Ho for RedOrbit.com



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