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American Trypanosomiasis

American trypanosomiasis, or Chagas disease, is caused by the parasite infection of Trypanosoma cruzi. This parasitic infection is present in a variety of regions, but is most common in isolated areas within the Americas. Our company is completely capable of assisting you in the development process of drugs and therapies for American trypanosomiasis.

Introduction to American Trypanosomiasis

American Trypanosomiasis is a parasitic infection caused by the protozoan Trypanosoma cruzi. Current estimates suggest that between 240,000 and 350,000 individuals in the US are infected with Chagas disease. This group primarily consists of immigrants from Mexico, Central and Southern America, as they are the regions where the disease is most easily contracted. Transmission of this disease is most commonly done through the feces of triatomine or kissing bugs.

Pathogenesis of American Trypanosomiasis

American Trypanosomiasis, also known as Chagas disease has several stages that make up its pathogenesis. First, the human body is penetrated by the Trypanosoma cruzi parasite via the bite and excrement of an infected triatomine bug. The parasites then invade tissues in the vicinity to which they were spawned and grow proliferatively within cells, which triggers an acute inflammatory response. The infection progresses further and the parasites spread through blood circulation to vital organs, especially the heart and intestines. Such chronic infections may cause irreparable bodily harm and inflammation, leading to megacolon, cardiac failure, or megaesophagus.

Transmission patterns of Trypanosoma cruzi.Fig. 1 Eco-epidemiological transmission patterns of Trypanosoma cruzi in Panama. (Rodriguez, I.G. and Loaiza, J.R., 2017)

Diagnosis Development of American Trypanosomiasis

There is a combination of monitoring and laboratory tests to be conducted for diagnosing American Trypanosomiasis. Chagas Disease is one such example. Polymerase Chain Reaction (PCR): This machine-based laboratory method enables detection s of parasitic DNA within blood, tissues or fluids at an extremely high accuracy which makes it a suitable tool for infection detection during both the acute and chronic stages. The minutest signs of parasitic DNA can be detected through PCR, which makes it 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 operates alongside clients to develop innovative therapy approaches for American Trypanosomiasis. Our support extends to the entire development cycle, as we aim to deliver the practical and efficient options needed.

Platforms of American Trypanosomiasis Therapy Development

Animal Models of American Trypanosomiasis

We specialize in developing and exploiting animal models that closely reproduce the clinical pathology and therapy responses of American Trypanosomiasis. These models allow us to test the safety and efficacy of potential therapies with accuracy.

Non-Genetically Engineering Models
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.
Optional Models
  • T. cruzi Infected Zebrafish Model
  • T. cruzi Infected Chronic Gastrointestinal Manifestation
  • T. cruzi Infected Dog chronic Chagas cardiomyopathy Model
  • T. cruzi Sexual Transmission Model
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.

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