50 years of research – Discovery of a promising treatment for Chagas disease

Chagas disease is a life-threatening disease caused by the protozoan parasite Trypanosoma cruzi.

Tens of millions of people in the Americas are affected by the disease, but there is no effective treatment.

Researchers at the University of Georgia have identified a potential treatment for Chagas disease, marking the first drug with the potential to effectively and safely target parasitic infection in more than 50 years.

AN15368, a drug with antiparasitic properties, will begin clinical trials in humans over the next few years.

“I’m very optimistic,” said Rick Tarleton, corresponding author of the study and UGA Athletic Association professor emeritus at Franklin College of Arts and Sciences. “I think this has a very strong chance of being a real solution, not just a substitute for something that works better than the drugs we have now.”

The new drug works by targeting the parasite that causes the disease, Trypanosoma cruzi (T. cruzi).

The parasite causes flu-like symptoms including fever, headache and vomiting in almost all of its victims. But once their immune response starts working, their symptoms may improve.

However, the infection can cause severe heart damage in 30-40% of individuals, which can be both debilitating and fatal.

The new drug is 100% effective in eliminating T. cruzi

Published in the journal Natural microbiology, the study found that the new drug was 100% effective in curing mice, as well as non-human primates naturally infected with the parasite at a research center in Texas. The animals also suffered no significant side effects from drug exposure.

Over the past few decades, previous treatment candidates have gone straight from experimental infections in mice to clinical trials in humans, where they have failed to cure the infection. The effectiveness of the new drug in non-human primates bodes well for its performance in humans.

“We have something that’s as close to effective as it gets in what’s as close to a human as it gets, and there are no side effects. It really reduces the risk when it comes to humans,” Tarleton said. “It doesn’t make it infallible, but it takes it a lot further.”

Current drugs to treat T. cruz infection are not ideal

T. cruzi is carried by blood-sucking insects known as kissing bugs. Insects can be found throughout North, Central and South America.

In addition to a nasty bite, the creatures carry the T. cruzi parasite, which is transmitted through their faeces. Victims can become infected when they unknowingly rub the insect’s droppings into their eyes, nose, or an open wound.

The infection can also be transmitted through organ transplants, from a pregnant person to their fetus, or through contaminated food. However, infections through these routes are less common.

The gold standard drugs used to treat Chagas aren’t terrible, Tarleton said, but they’re not ideal. They can cause serious side effects and are not reliably effective, but they are currently the only treatment option.

Patients must also take the drugs for two months. And even common but mild side effects like headaches or nausea get old after a few weeks. As a result, about one in five people being treated for the disease stop taking their medication before they have a chance to cure the infection.

“Also, they have variable effectiveness, and that’s not predictable,” Tarleton said. “I think most doctors in Latin America have to say, ‘We have medicine. This is going to hurt you, and two months later after finishing it, we can’t really tell you if it worked or not.

“It’s really not a good incentive to take the drug.”

Chagas disease common in Latin American countries

Tens of millions of people across the Americas are infected with the parasite that causes Chagas disease. But it doesn’t get much media attention.

It’s most common in Latin American countries, especially in low-income areas where housing isn’t ideal. Some of the countries with the highest rates of the disease are Bolivia, Venezuela, Argentina, Chile, Mexico and Brazil.

In homes with thatched roofs, mud walls, or inadequate protection from the elements, kissing insects thrive, making infection more likely.

Chagas disease poses a significant risk to pets

The Centers for Disease Control and Prevention estimates that about 300,000 people infected with the parasite currently live in the United States. But because the disease isn’t a huge threat in places with good housing options, the treatment and prevention of Chagas disease doesn’t receive much research funding.

We are increasingly concerned about the T. cruzi infection rates among outdoor pets in the United States, however. Working dogs and other pets that spend long periods outdoors contract the parasite at an alarming rate.

“There are areas where infection rates are 20% to 30% new infections per year,” Tarleton said. “These are usually serious infections where dogs die or develop a disease that renders them unable to work.”

Tarleton hopes to partner with veterinary pharmaceutical companies in the future to create a drug to treat the infection in companion animals to fund diagnostics and drug purchases in Latin America.

Reference: “Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates” by Angel M. Padilla, Wei Wang, Tsutomu Akama, David S. Carter, Eric Easom, Yvonne Freund, Jason S. Halladay, Yang Liu, Sarah A. Hamer, Carolyn L. Hodo, Gregory K. Wilkerson, Dylan Orr, Brooke White, Arlene George, Huifeng Shen, Yiru Jin, Michael Zhuo Wang, Susanna Tse, Robert T. Jacobs and Rick L. Tarleton, September 5, 2022, Natural microbiology.
DOI: 10.1038/s41564-022-01211-y

Comments are closed.