Sleeping Sickness Treatment Found in Cancer Drug

Kojo Mensa-Wilmot (University of Georgia)

31 August 2016. An experimental drug designed to treat solid tumor cancers was shown in lab tests to rid mice of human African trypanosomiasis, also known as sleeping sickness. The findings of a team from University of Georgia in Athens, Northeastern University in Boston, and the biotechnology company Cleveland BioLabs Inc. appear in the 26 August issue of the journal Scientific Reports.

The researchers, led by Georgia cellular biology professor Kojo Mensa-Wilmot, are seeking more effective and easily administered drugs to treat human African trypanosomiasis, a disease that occurs in 36 sub-Saharan Africa countries and in 2014 affected nearly 3,800 people, according to World Health Organization. The disease is caused by infections from Trypanosoma brucei parasites, single cell organisms transmitted by tsetse flies found largely in rural regions.

Symptoms begin with fever, headaches, joint pains, and itching, but once the infection crosses the blood-brain barrier, can result in confusion, sensory disturbances, poor coordination, and disturbances in sleep cycles. The disease can also be fatal.

The authors report 5 drugs are now available for treating human African trypanosomiasis, or HAT, but all must be given with injections of eflornithine. As a result, treating the disease requires visits to a clinic, often a difficult task in isolated rural areas. In addition, the authors report only two treatments for HAT in drug companies’ pipelines.

“HAT is a disease of poverty,” says Mensa-Wilmot in a university statement, “so there is little motivation for the pharmaceutical industry to be heavily invested. Because the parasite can become drug resistant, it is very important for us to be vigilant in finding new effective, orally administered treatments for the disease.”

To short-cut the sometimes extended drug discovery process, Mensa-Wilmot and colleagues employed a strategy of finding existing compounds that could treat HAT infections with established safety profiles progressing at least to clinical trials. Among the drugs screened were a class of compounds known as curaxins, small-molecule drugs being developed by Cleveland BioLabs in Buffalo, New York as cancer therapies.

Curaxins work by blocking the expression of genes that produce proteins needed for tumors to survive, and can be applied to a number of solid tumor cancers. And because they do not destroy DNA, curaxins may also be safer to use than chemotherapy. In their review, the team found curaxins targeted the chemical structure of genes, similar to that of the parasites causing HAT infections. Chemical screening of 26 curaxin compounds returned 22 with potential potency against the parasites in the blood stream.

Tests of the 3 most potent curaxins in lab mice infected with HAT parasites show the compound, code-named CBL0137 by Cleveland Biolabs rid all of the mice of their infections, preventing the parasite cells from dividing, and thus proliferating in the body. CBL0137 is also being tested in an early-stage clinical trial for safety and to determine recommended doses among individuals with solid tumor cancers.

The authors believe this strategy of repurposing current drug compounds offers a faster and more economical method of drug discovery, which in this case could lead to a new oral drug for HAT and other tropical diseases caused by parasites.

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