Compounds for the treatment of sleeping sickness

The CSIC, in collaboration with the Katholieke Universiteit Leuven and Toyama Prefectural University, has developed a series of compounds for the prevention and treatment of parasitic diseases such as leishmaniasis and sleeping sickness, caused by kinetoplastids.

 

TrypanosomaBrucei ProcyclicTrypomastigote SEM, by Zephyris - Own work. Creative Commons. Wikimedia CommonsThe protozoan parasite Trypanosoma brucei is the etiologic agent of African trypanosomiasis (sleeping sickness in human or nagana in domestic livestock). The chemotherapy of African trypanosomiasis relies on a few drugs which have adverse side-effects. Drug resistance and the limited number of alternatives of treatment clearly justify the need for new drugs that are safe, effective and affordable.

The CSIC, in collaboration with the Katholieke Universiteit Leuven and Toyama Prefectural University, has developed a series of compounds for the prevention and treatment of sleeping sickness. The compounds, peptide carbohydrate binding agents (CBAs), are able to specifically interact with surface glycoproteins of the parasite, giving rise to toxic events and cell death.

Carbohydrate-binding agents (CBAs) had been proposed previously as an original therapeutic concept against various viral infections, such as human immunodeficiency virus (HIV) and human hepatitis C virus.

In the case of trypanosomes, CBAs can provide therapeutic potential by binding to surface glycoproteins of the parasite and impairing its normal function. The cell surface of bloodstream Trypanosoma brucei is covered by a densely packed coat of glycoproteins, which physically protect underlying proteins from the host immune system.

One CBA tested in a mouse model of sleeping sickness renders parasitological cure when administered during a four day period

The scientists have identified non-peptidic mannose-binding agents from prokaryotic origin with inhibitory activity against fungi, yeast and several viruses including HIV and hepatitis C. They have tested the efficacy of one CBA in a mouse model of sleeping sickness, and have found out that this agent has no toxicity and renders parasitological cure when administered during a four day period. The fact that the CBAs identified are microbial natural products, enables obtaining new structurally closely related compounds by fermentation easily.

Moreover, the strategy can be useful for the treatment of other diseases, as it has been demonstrated that some carbohydrate binding agents are able to specifically interact with these surface glycoproteins and give rise to toxic events in more kinetoplastids (group of protozoa that includes parasites responsible for diseases like sleeping sickness as well as Chagas disease and leishmaniasis).

Contact:

José Ramón Domínguez Solís,
Vicepresidencia Adjunta
de Transferencia de Conocimiento (CSIC)
Tel.: + 34 – 95 423 23 49
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