SAN FRANCISCO, Calif.--Researchers at the San Francisco Veterans Affairs Medical Center and UC San Francisco have demonstrated that a type of drug known as a cysteine protease inhibitor may be highly effective against American trypanosomiasis or Chagas1 disease, which is caused by an infection with the parasite Trypansoma cruzi (T. cruzi).

Chagas is the leading cause of heart disease in Latin America and approximately 50,000 people die every year as a result of it. Once confined to Latin America, cases of Chagas1 disease have been reported in the United States. The study provides proof that this new class of protease inhibitors can be safely used in animals to treat a parasitic infection, the researchers said.

The study, published in the August 17 issue of the Journal of Experimental Medicine, reports on the treatment of 21 mice infected with lethal doses of T. cruzi. All of the treated mice were rescued from the infection. A control group of untreated mice all died within four to ten days. Some of the treated mice were followed for as long as a year with no evidence of disease or parasites.

Importantly, the cysteine protease inhibitors produced no side-effects in the animals, and there was no indication of drug resistance. According to senior author James H. McKerrow, MD, PhD, director of the National Institutes of Health-sponsored Tropical Disease Research Unit at the San Francisco VA Medical Center, and UCSF professor of pathology and pharmaceutical chemistry, the study demonstrates in mice that cysteine protease inhibitors stop T. cruzi from replicating by 3turning off2 a specific enzyme critical to the parasite1s survival -- much like aspartate protease inhibitors work against Human Immunodeficiency Virus (HIV).

Because cysteine and aspartate protease inhibitors function in similar ways, the researchers are optimistic about the drug1s safety and efficacy in humans.

While its potential as a Chagas treatment is very encouraging, perhaps
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Contact: James Larkin
jlarkin@itsa.ucsf.edu
(415) 750-6633
University of California - San Francisco
18-Aug-1998