Memantine, a drug used in Alzheimer’s patients, may be effective for treating Chagas disease, according to a study by the Institute of Biomedical Sciences (ICB) of University of São Paulo (USP) and published in the scientific journal PLOS Neglected Tropical Diseases.
The results showed that the substance is capable of killing the parasite that causes the disease, Trypanosoma cruzi, usually transmitted through barber insect bites. In tests on infected mice, the amount of parasites was considerably reduced after memantine treatment and the survival rate of the animals increased.
As Professor Ariel M. Silber, the study’s coordinator, explains, the next step is to verify whether the data collected allow a clinical trial to be conducted to test whether treatment with memantine would have the same effect on humans.
The World Health Organization (WHO) estimates that the current number of people infected with T. cruzi is between 6 and 7 million, mostly in Latin America. Once in the body, the parasite causes inflammatory reactions that can compromise the functioning of tissues and organs.
Chagas disease is part of the so-called “neglected diseases”, a category that covers a set of treatable and curable but endemic diseases in low-income populations. As these diseases affect group low-income populations, the pharmaceutical industry is not motivated in invest in their research.
Existing treatment is unsatisfactory
There are currently two drugs used to treat Chagas, nifurtimox and benznidazole, which are very effective in the acute form of the disease. However, both are toxic to humans, so they have serious side effects when prolonged use is required to treat the chronic form of the disease.
According to Silber, most people abandon the treatment due to the side effects. “This is why it is so important to have new medicines,” Silber said.
In the human organism, the action of memantine occurs from the interaction with NMDA (N-methyl D-Aspartate) receptors. The researchers identified in previous studies that Trypanosoma cruzi has receptors with similar characteristics. Thus, they raised the hypothesis that the drug could interact in the same way if applied to the parasite, which was eventually proved; and in the case of Trypanosoma cruzi, this interaction ultimately causes its death.
The results showed that the parasite died with a relatively low dose of memantine, while cells infected with it were little or not affected. This process was detailed in the master’s dissertation of one of the members of the team, Flávia Silva Damasceno’s. Later, the study was deepened in the dissertation of another member, Higo Fernando Santos Souza, who corroborated the hypothesis and generated the latest article published.
The fact that memantine is already used in humans is a great advantage for the development of a new drug. “We already know, for example, what is the maximum dose that can be used in an infected patient, the possible side effects, the speed at which the body eliminates the substance. There is a lot of accumulated knowledge about the drug that may be of value for use in treating Chagas disease,” says Silber.