Division of Microbiology and Infectious Diseases (DMID)

Chagas' Disease Therapeutic Candidate: K777

NIAID is supporting studies of K777, a potential new therapeutic for treating Chagas' disease, a parasitic infection caused by T. cruzi. Credit: CDC

Chagas’ disease is caused by the parasite Trypanosoma cruzi, which is transmitted to animals and people through the fecal matter of insect vectors known as triatomine bugs, or “kissing bugs.” Left untreated, Chagas’ disease can cause serious heart and digestive problems. Treatment of Chagas’ disease focuses on killing the parasite in acute infection and managing signs and symptoms in later stages. Chagas’ disease (T. cruzi infection) is also referred to as American trypanosomiasis.

Approximately 8–10 million persons are infected with Chagas’ disease throughout Latin America, with approximately 50,000 deaths per year. Chagas’ disease was once entirely confined to the Region of the Americas—principally Latin America—but it has now spread to other continents (World Health Organization).

There are only two available therapies for treatment of Chagas’ disease: benznidazole and nifurtimox. Significant toxicities are associated with each of these drugs. Safer, more effective therapies for treatment of Chagas’ are urgently needed. NIAID-supported investigators have identified K777 as a potent inhibitor of cruzain, a cysteine protease essential for the parasite.

Multiple Stages of K777 Development Supported by NIAID

NIAID supported basic research that led to identification of K777 as a potential candidate for treating Chagas’ disease. Support of this project through NIAID/DMID grants and preclinical services included drug synthesis, as well as studies of toxicity, dosing, and metabolism. For advanced development, NIAID/DMID support included substance manufacturing, formulation, pharmacokinetic studies, and repeat toxicity, dosing, and safety studies.

New Diagnostics and Treatments for Chagas’ Hold Promise

NIAID/DMID will continue to support studies of K777 to determine its safety and efficacy for treating Chagas’ disease. Together with ongoing clinical trials of antifungal drugs for Chagas’ treatment and the recent approval of an in vitro enzyme strip assay (ESA) as a supplemental test to detect antibodies to T. cruzi, diagnosis and treatment of Chagas’ disease could change dramatically in the next few years.