The drugs currently used to treat Chagas disease, a neglected tropical disease, have serious side effects and limited use in those with chronic disease. Now, researchers have reported in PLOS Neglected Tropical Diseases that memantine, a drug currently used to treat Alzheimer's disease, can diminish the number of parasites in mice with Chagas disease, and increase the survival rate of the animals.
Chagas disease, caused by the protozoan Trypanosoma cruzi affects 5 to 6 million people in the Americas. The disease can be divided into acute and chronic phases, with the clinical phase causing heart, esophagus or intestinal symptoms. The two drugs that have been used to treat Chagas for the last 50 years--nifurtimox and benznidazole--are highly effective in the acute phase but used sparingly in the chronic phase due to serious side effects that occur with long-term treatment.
In the new work, Ariel M. Silber of Universidade de São Paulo, Brazil, and colleagues studied memantine, which works on the central nervous system of animals but has also been shown to kill protozoa. The researchers first studied the effect of different concentrations of memantine on cultured macrophages-- a type of white blood cell--that were infected with T. cruzi. Next, they tested the drug in T. cruzi-infected mice.
The team found that memantine reduced the number of T. cruzi-infected macrophages in a dose-dependent way; more drug led to a greater reduction in the infection. In mice with Chagas disease, memantine lowered levels of the parasite by 40% and increased survival rates from 7.5% to 12.5%. The mice treated with memantine also had 35.3% lower parasite levels in their hearts compared to control animals.
"All these findings point memantine as an interesting starting point for the development of an optimized alternative therapy for Chagas disease," the researchers say.
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Citation: Santos Souza HF, Rocha SC, Damasceno FS, Rapado LN, Pral EMF, et al. (2019) The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi. PLOS Neglected Tropical Diseases 13(9): e0007226. https:/
Funding: This work was supported by: Fundação de Amparo à Pesquisa do Estado de São Paulo grant 2016/06034-2 (awarded to AMS), (http://www.
Competing Interests: The authors have declared that no competing interests exist.