American Trypanosomiasis
American trypanosomiasis, commonly referred to as Chagas disease, is a parasitic infection caused by Trypanosoma cruzi. This tropical disease is widespread in the Americas, especially in isolated regions of Latin America. Our company is fully prepared to support your needs in developing drugs and therapies for American trypanosomiasis.
Introduction to American Trypanosomiasis
American Trypanosomiasis is a parasitic infection caused by the protozoan Trypanosoma cruzi. It is estimated that between 240,000 and 350,000 people in the United States are infected with Chagas disease. This population is predominantly composed of immigrants from regions where the disease is endemic, such as Mexico, Central America, and South America. The disease is primarily transmitted through the feces of triatomine bugs, commonly known as kissing bugs.
Pathogenesis of American Trypanosomiasis
The pathogenesis of American Trypanosomiasis, or Chagas disease, involves several stages. Initially, Trypanosoma cruzi parasites enter the human body through the bite of an infected triatomine bug, which defecates near the bite wound or mucous membranes. The parasites then invade local tissues and proliferate intracellularly, causing an acute inflammatory response. As the infection progresses, the parasites disseminate via the bloodstream to various organs, particularly the heart and gastrointestinal tract. Chronic infection can lead to significant tissue damage and inflammation, resulting in cardiomyopathy, megacolon, and megaesophagus.
Fig. 1 Eco-epidemiological transmission patterns of Trypanosoma cruzi in Panama. (Rodriguez, I.G. and Loaiza, J.R., 2017)Diagnosis Development of American Trypanosomiasis
The diagnosis of American Trypanosomiasis (Chagas Disease) relies on observation and laboratory tests. Polymerase Chain Reaction (PCR): Detects trypanosomal DNA in blood, tissue, or bodily fluids with high sensitivity and specificity, suitable for both acute and chronic phase diagnosis. PCR can detect very low levels of parasitic DNA and is considered the gold standard in molecular diagnostics.
Drug Targets of American Trypanosomiasis
- Carbonic Anhydrase (TcCA) Inhibitors
Sulfonamides, Thiols, and Hydroxamates: TcCA is crucial for parasite survival, influencing ion exchange and growth. Several inhibitors have been discovered, showing trypanocidal effects in vitro.
- Tc80 Proteinase and Peptides
Prolyl oligopeptidase (Tc80): Secreted by the parasite, this enzyme is involved in cell invasion. Peptidyl nitrile and Peptidyl ketobenzothiazole are competitive inhibitors of Tc80.
- Proteasome Inhibitors
GNF6702 and GSK3494245: These inhibitors target the proteasome, crucial for protein degradation in the parasite. GNF6702 has shown promising results against kinetoplast diseases, including Chagas.
- Ergosterol Pathway and CYP51 Inhibitors
Sterol 14-alpha demethylase (CYP51): An enzyme essential for the parasite's viability. Anti-fungal triazole derivatives, such as ravuconazole and posaconazole, have been tested as inhibitors but have shown limited sustained efficacy in clinical trials.
- Cysteine Peptidase and K777
Cruzipain: A lysosomal cysteine peptidase. K777, a vinyl sulfone derivative, has shown significant reduction in parasite-induced heart damage in vivo.
Our Services
Our company adopts a collaborative approach, partnering closely with clients to create tailored and innovative therapy strategies for American Trypanosomiasis. We offer comprehensive support throughout the entire development process, ensuring effective and customized solutions.
Platforms of American Trypanosomiasis Therapy Development
Animal Models of American Trypanosomiasis
We have extensive experience in creating and utilizing animal models that faithfully mimic the disease traits and therapeutic reactions of American Trypanosomiasis. These models enable us to evaluate the safety and effectiveness of prospective therapies with precision.
| Non-Genetically Engineering Models | ||
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| We provide an array of models designed to meet specific research requirements for American Trypanosomiasis. These models allow researchers to replicate and study the intricate biological processes associated with the disease. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition, we offer a range of comprehensive animal model services that concentrate on specific signaling pathways and molecular targets.
If you are interested in our services, please contact us at your earliest convenience for more information.
References
- Rodriguez, I.G. and Loaiza, J.R., "American trypanosomiasis, or Chagas disease, in Panama: a chronological synopsis of ecological and epidemiological research." Parasit Vectors, (2017). 10(1): p. 459.
- Francisco, A.F., et al., "Challenges in Chagas Disease Drug Development." Molecules, (2020). 25(12).
- Chatelain, E. and Scandale, I., "Animal models of Chagas disease and their translational value to drug development." Expert Opin Drug Discov, (2020). 15(12): p. 1381-1402.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.