Saturday, September 10, 2011

A Potentially New Therapy for Chagas Disease, a Parasitic Infection

Chagas disease is the result of an infection caused by the parasite, Trypanosoma cruzi.  The vector for this parasite is the so-called assassin bug or kissing bug that targets its hosts for blood, usually at night.  The parasite is usually transmitted through the insect's feces.  Millions of people in Latin America carry this parasite.  In addition, the United States and Spain have reported the highest incidences of this disease outside of Latin America.  Furthermore, the World Health Organization (WTO) has estimated that ten million people worldwide are infected with this parasite. 


The symptoms are somewhat benign at the early stages of infection.  Unfortunately, the parasite persists within the body for years or decades and can ultimately lead to serious damage to the heart, often resulting in death.


The current drugs available to treat this disease – nifurtimox and benznidazole - are outdated and of little value.  In addition to their serious side effects, their efficacy depends upon a 60 to 90 day course of treatment – this requirement makes their use highly impractical. 


In regards to the etiology of the disease, there is a crucial enzyme, cruzain, that is a necessary component in the life cycle of Trypanosoma cruzi.  Cruzain belongs to a class of enzymes referred to as proteases – enzymes that catalyze the degradation of proteins.  Doctor James McKerrow, a biochemist at the University of California, was in search of a suitable inhibitor of this enzyme.  He enlisted the help of his colleague Doctor Jim Palmer, a chemist who had synthesized a number of protease inhibitors when he was at Khepri Pharmaceuticals in San Francisco.  In response to this request, Palmer synthesized a potent version of an inhibitor that effectively led to the death of the parasites grown in the laboratory.


This is an exciting development that has captured the attention of the Food and Drug Administration (FDA) that has approved a phase I safety trial of the compound referred to as K777.