Alzheimer’s Drug Reduces Chagas Disease Infection in Mice
Alzheimer’s Drug Reduces Chagas Disease Infection in Mice

Alzheimer’s Drug Reduces Chagas Disease Infection in Mice

The drug, called memantine, could enter clinical trials to determine its effectiveness in humans.

Dec 1, 2019
Emily Makowski

ABOVE: An Alzheimer’s drug reduces infection in murine macrophages infected with Trypanosoma cruzi (blue dots).
ARIEL SILBER

EDITOR’S CHOICE IN DISEASE & MEDICINE

The paper

H.F. Santos Souza et al., “The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi,” PLOS Negl Trop Dis, 13: e0007226, 2019.

In 2014, researchers led by Ariel Mariano Silber at the University of São Paulo in Brazil showed that the Alzheimer’s drug memantine killed Trypanosoma cruzi, the parasite that causes Chagas disease, in vitro. Now, Silber and his colleagues report evidence that the treatment can reduce T. cruzi infection in mice and in cultured murine macrophages, suggesting it might be a viable option for patients in parts of Central and South America where Chagas is widespread.

The two drugs currently used to treat Chagas disease, nifurtimox and benznidazole, are most effective early on, often before patients realize they are infected. “Most of the time, patients assume that [the disease] is something else, like the flu, so they don’t go to the doctor for a diagnosis,” Silber tells The Scientist. By the time the disease progresses, he says, the drugs are less effective, and patients can develop severe cardiomyopathy. The drugs also have significant side effects.

In the new study, the researchers treated T. cruzi–infected mice with memantine and found that the mice had fewer parasites in their blood and hearts, fewer inflammatory cells involved in the immune system’s infection response, and an increased survival rate compared with untreated mice. In vitro experiments showed the drug was clearing the parasite from infected macrophages. Silber hopes to set up clinical trials of the drug, which has few side effects in humans, in the future.

Nuclei of a noninfected macrophage (left), a macrophage infected with Trypanosoma cruzi (center; small blue spots correspond to the nuclei of the parasites), and an infected macrophage that has been treated with memantine and thus harbors fewer parasites (right).
ARIEL SILBER

Bianca Silvana Zingales, a biochemist at the University of São Paulo who has collaborated with Silber in the past but was not involved with the current study, says that while “memantine represents a promising candidate for Chagas disease,” the current study focused on just one strain of the parasite, and future work should include other strains. “T. cruzi strains have extensive genetic and biological differences, including different susceptibilities to drugs,” she says.

Emily Makowski is an intern at The Scientist. Email her at emakowski@the-scientist.com.