Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Cruzipain Inhibitors Show Potential for Treatment of Chagas Disease

By BiotechDaily International staff writers
Posted on 08 Jan 2014
Image: Trypanosoma cruzi in blood smear from patient with trypanosomiasis (Photo courtesy of the CDC – [US] Centers for Disease Control and Prevention).
Image: Trypanosoma cruzi in blood smear from patient with trypanosomiasis (Photo courtesy of the CDC – [US] Centers for Disease Control and Prevention).
A new generation of antiparasitic drugs based on inhibitors of the enzyme cruzipain has been shown to have potential for more effective treatment of the chronic form of Chagas disease.

Chagas disease or American trypanosomiasis, caused by the parasite Trypanosoma cruzi, affects about 18 million people living mostly in Latin America.

The current drug of choice for treating Chagas is benznidazole. Its mechanism of action is the production of free radicals, to which the T. cruzi is particularly sensitive. Benznidazole has a significant activity during the acute phase of the disease, with a success rate of up to 80%. Its curative capabilities during the chronic phase are, however, limited. Some studies have found parasitologic cure (a complete elimination of T. cruzi from the body) in pediatric and young patients during the early stage of the chronic phase, but overall failure rate in chronically infected individuals is typically above 80%.

Investigators at the Merck Frosst Center for Therapeutic Research (Kirkland, QC, Canada) focused on a different approach to killing T. cruzi: inhibition of the enzyme cruzipain. This enzyme is a cysteine proteinase that hydrolyzes chromogenic peptides at the carboxyl arginine or lysine residue. It requires at least one more amino acid between the terminal arginine or lysine and the amino-blocking group. The purified enzyme digests itself. The enzyme plays a critical role in the development and differentiation of T. cruzi.

The investigators treated mice with acute T. cruzi infection with oral doses of two key cruzipain inhibitors, Cz007 and Cz008, in chow for 28 days. Parasite presence in blood, heart, and esophagus was evaluated.

Results published in the December 9, 2013, online edition of the journal Antimicrobial Agents and Chemotherapy revealed that based on negative qPCR in all three tissues, cure rates in surviving animals were 90% for Cz007, 78% for Cz008, and 71% for benznidazole, the control compound.

"The efficacy shown in these T. cruzi murine studies suggests that nitrile-containing cruzipain inhibitors show promise as a viable approach for a safe and effective treatment of Chagas disease," said senior author Dr. Deborah Nicoll-Griffith, a researcher at the Merck Frosst Center for Therapeutic Research. "While historically infection was largely confined to poor and rural populations in Central and South America, it has been emerging in the US, Canada, Europe, Japan, and Australia, due to immigration, and nonvectorial transmission is becoming a public health threat."

Related Links:

Merck Frosst Center for Therapeutic Research




Channels

Genomics/Proteomics

view channel
Image: Transmission electron micrograph of norovirus particles in feces (Photo courtesy of Wikimedia Commons).

Norovirus Interacts with Gut Bacteria to Establish a Persistent Infection That Can Be Blocked by Interferon Lambda

A team of molecular microbiologists and virologists has found that norovirus requires an intimate interaction with certain gut bacteria to establish a persistent infection, and that the infective process... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.