-
Drug found for parasite that is major cause of death worldwide
May 21, 12 Drug NewsResearch by a collaborative group of scientists from UC San Diego School of Medicine, UC San Francisco and Wake Forest School of Medicine has led to identification of an existing drug that is effective against Entamoeba histolytica. This parasite causes amebic dysentery and liver abscesses and results in the death of more than 70,000 people worldwide each year.
Using a high-throughput screen for drugs developed by the research team, they discovered that auranofin - a drug approved by the US Food and Drug Administration 25 years ago for rheumatoid arthritis - is very effective in targeting an enzyme that protects amebae from oxygen attack (thus enhancing sensitivity of the amebae to reactive oxygen-mediated killing).
The results of the work, led by Sharon L. Reed, MD, professor in the UCSD Departments of Pathology and Medicine and James McKerrow, MD, PhD, professor of Pathology in the UCSF Sandler Center for Drug Discovery, will be published in the May 20, 2012 issue of Nature Medicine.
Entamoeba histolytica is a protozoan intestinal parasite that causes human amebiasis, the world’s fourth leading cause of death from protozoan parasites. It is listed by the National Institutes of Health as a category B priority biodefense pathogen. Current treatment relies on metronidazole, which has adverse effects, and potential resistance to the drug is an increasing concern.
“Because auranofin has already been approved by the FDA for use in humans, we can save years of expensive development,” said Reed. “In our studies in animal models, auranofin was ten times more potent against this parasite than metronidazole.”
Entamoeba Histolytica - Amoebiasis
Entamoeba histolytica is a protozoan parasite responsible for a disease called amoebiasis. It occurs usually in the large intestine and causes internal inflammation as its name suggests (histo = tissue, lytic = destroying). 50 million people are infected worldwide, mostly in tropical countries in areas of poor sanitation. In industrialized countries most of the infected patients are immigrants, institutionalized people and those who have recently visited developing countries.
Inside humans Entamoeba histolytica lives and multiplies as a trophozoite. Trophozoites are oblong and about 15–20 µm in length. In order to infect other humans they encyst and exit the body. The life cycle of Entamoeba histolytica does not require any intermediate host. Mature cysts (spherical, 12–15 µm in diameter) are passed in the feces of an infected human. Another human can get infected by ingesting them in fecally contaminated water, food or hands. If the cysts survive the acidic stomach, they transform back into trophozoites in the small intestine. Trophozoites migrate to the large intestine where they live and multiply by binary fission. Both cysts and trophozoites are sometimes present in the feces. Cysts are usually found in firm stool, whereas trophozoites are found in loose stool. Only cysts can survive longer periods (up to many weeks outside the host) and infect other humans. If trophozoites are ingested, they are killed by the gastric acid of the stomach. Occasionally trophozoites might be transmitted during sexual intercourse.
In a mouse model of amebic colitis and a hamster model of Amebic liver abscess, the drug markedly decreased the number of parasites, damage from inflammation, and size of liver abscesses.
“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,” said Reed. The drug has been granted “orphan-drug” status (which identifies a significant, newly developed or recognized treatment for a disease which affects fewer than 200,000 persons in the United States) and UC San Diego hopes to conduct clinical trials in the near future.
Amebic Dysentery Overview
What is amebic dysentery?
A person with amebic dysentery has an infection in the intestines that is caused by a parasite called Entamoeba histolytica. This condition can be spread through food or water that is contaminated with stools. Amebic dysentery is most common in tropical areas but can be seen anywhere in the world. This illness normally lasts about 2 weeks, but if not treated is can reoccur. When amebic dysentery spreads beyond the intestines to other parts of the body (such as the liver, lung, or brain) it is referred to as extraintestinal amebiasis. Amebic dysentery infections are most severe in the very young, the elderly, and in those who may be taking daily corticosteroids.What are the symptoms of amebic dysentery?
The symptoms of amebic dysentery usually develop 2 to 4 weeks following exposure to the parasite. The symptoms of amebic dysentery include malaise, generalized weakness, abdominal tenderness, abdominal pain, abdominal cramping, abdominal swelling, diarrhea (watery stools), excessive gas, fatigue, fever, vomiting, bloody stool, rectal pain, unintentional weight loss.
How does the doctor treat amebic dysentery?
Treatment for amebic dysentery may include oral antiparasitic medication for about 10 days depending upon the severity of the infection. The stool should be rechecked following the completion of the oral medication to make sure the infection is completely gone. Surgery may be needed to treat complications such as liver abscess, perforated bowel, and massive gastrointestinal bleeding.###
Additional contributors to the study include first author Anjan Debnath, Shamila S. Gunatilleke and James H. McKerrow, UCSF Sandler Center for Drug Discovery; Derek Parsonage and Leslie B. Poole, Wake Forest School of Medicine; Rosa M. Andrade, Chen He, Eduardo R. Cobo and Ken Hirata, UC San Diego School of Medicine; Steven Chen and Michelle R. Arkin, UCSF; Guillermina GarcÃa-Rivera, Esther Orozco and Máximo B. MartÃnez, Instituto Politécnico Nacional, Mexico City; and Amy M. Barrios, University of Utah, Salt Lake City.This work was supported by the Sandler Foundation and US National Institute of Allergy and Infectious Diseases grant 5U01AI077822-02, with additional support from R01 GM050389.
###
Scott LaFee
.(JavaScript must be enabled to view this email address)
619-543-6163
University of California - San DiegoAlso in this section:
Subscribe to the "News" RSS Feed 
TOP ۞
