One protein inhibitor could treat Chagas, leishmaniasis and sleeping sickness

Tsetse fly from Burkina Faso--Courtesy of IAEA CC BY-SA 4.0

Wellcome Trust-backed scientists have found a compound that treats three neglected parasitic diseases in mice: leishmaniasis, Chagas disease and sleeping sickness.

The trio of diseases affects millions of people in Latin America, Asia and Africa, yet current treatments are limited and have a number of side effects. The Wellcome-funded team from the Novartis Research Foundation’s Genomics Institute (GNF) focused on the genetic and biological similarities between the “kinetoplastids,” single-celled parasites that cause the diseases.

Because of these similarities, the researchers sought a compound that would be effective against all three diseases. After testing more than 3 million chemicals, they landed on a compound dubbed GNF6702, which destroyed the parasites in mice and did not harm human cells in lab tests, according to a statement. The drug works by selectively inhibiting a protein complex inside kinetoplastids called the proteasome. It does not harm the mice as it does not inhibit the mammalian proteasome.

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"We found that these parasites harbour a common weakness,” said GNF’s Frantisek Supek, a research investigator and senior author, in the statement. "We hope to exploit this weakness to discover and develop a single class of drugs for all three diseases."

Because the compound did not cause adverse effects in mice, the team is hopeful that it may have fewer side effects in humans than current drugs. GNF6702 is now being tested for toxicity before it can be advanced to human studies.

There are limited treatments for the diseases, including the use of antiparasitic treatment against Chagas, which can cause side effects including peripheral neuropathy, insomnia, vertigo, and anorexia and weight loss. As for sleeping sickness, it is important to diagnose and treat the disease early, before it reaches the neurological stage and the blood-brain barrier comes into play.

- here's the statement
- see the abstract

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