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Chagas Disease: Complications in The Esophagus can be Hereditary, According To a Study

Research led by Brazilian scientists determined that the genetic mutation may be linked to disorders in patients with Chagas disease. This condition is caused by Chagas disease and causes the esophagus to become inflamed. For researchers, the survey findings may inspire new treatments for people with this condition.

Observations indicate that in carriers of these mutations, increased production of an inflammatory mediator known as IFN-gamma leads to dysfunction of mitochondria (responsible for energy generation) in neurons.

Thus, the degeneration of neurons present in the wall of the esophagus will contribute to the esophageal progression associated with Chagas disease. Mitochondrial changes were found in 18% of patients with chronic Chagas heart disease, but only in 2% of the Brazilian population overall.

“After years of research, we have been able to better understand the mechanism of mitochondrial dysfunction caused by IFN-gamma. The importance of this finding lies precisely in the fact that we can look for specific drugs to reduce this alteration”, explains Prof. Ediseo Konia Neto .

Heart Problem

The specialist, who is also a researcher at the Instituto do Coração (InCor), says that inflammatory changes have already been demonstrated in patients with cardiomyopathy, a cardiac complication also associated with Chagas disease.

The researchers analyzed material taken from the organs of patients with Chagas disease who had undergone a heart transplant. After that, they noticed a disturbance in the energy metabolism of the organ – there was a decrease in a large number of proteins and enzymes involved in the production of ATP, which is the main form of chemical energy in the cell.

Through various analyses, it was possible to demonstrate that elevated IFN-gamma levels in patients with Chagas disease-induced cardiomyopathy reduce cellular energy metabolism, leading to mitochondrial dysfunction in cardiac tissue.

“By treating these heart muscle cells with IFN-gamma, we were able to observe a decrease in ATP production. Therefore, we hypothesized that IFN-gamma might also act on other forms of disease symptoms, decreasing the mitochondrial function. We set ourselves an esophageal case study”, adds Cunha Neto.

Current Search

In the research that has just been published, the group sequenced part of the genes of 13 patients with megaesophagus caused by Chagas disease. Of the people with digestive problems, about 40% had the same mitochondrial variant.

Through blood samples from patients, cells capable of reproducing indefinitely with the exact genetic makeup of the patient were isolated. The scientists used these modified and non-transformed cells to assess the effect of IFN-gamma on mitochondrial function.

The result was that the patients with the mitochondrial mutation produced less ATP in the presence of IFN-gamma than the cells of the patients without the mutation.

Among the substances that can be used for the treatment of the esophagus and cardiomyopathy are metformin, an oral antidiabetic, and resveratrol, which is found in plants with an antioxidant effect. Both were able to mitigate IFN-γ-induced mitochondrial dysfunction in cardiac cells.

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