• Wed. Feb 28th, 2024

New targets identified for the treatment of schistosomiasis

New targets identified for the treatment of schistosomiasis

Researchers from Brazil have discovered that the survival of the parasitic worm that causes schistosomiasis depends on the expression of a specific type of RNA. In animal experiments, blocking the molecule prevented infection.

Researchers at the Butantan Institute in São Paulo, Brazil, have made an important breakthrough in the fight against schistosomiasis. The team discovered a way to interrupt the reproductive cycle of parasitic worms (Schistosoma mansoni) responsible for the disease, potentially leading to a new therapeutic approach. Their findings were published PLOS Pathogenshighlight the important role of long non-coding RNAs (lncRNAs) in parasite survival, making them a promising target for future therapeutic strategies.

Schistosomiasis, caused by parasitic worms, affects 200 million people worldwide and has remained a major health challenge for decades. A peculiarity of these worms is that the adult male and female must remain paired throughout their lives for successful reproduction. Female worms can produce up to 3,000 eggs per day, about half of which reach the host’s intestines or bladder, while the rest are carried by the bloodstream to the liver and spleen, causing inflammation and liver cirrhosis, which ultimately leads to death.

A research team led by Professor Sergio Verjovski-Almeida of the University of São Paulo and Butantean Institute has launched a thematic project supported by FAPESP to explore the role of lncRNAs in human cancer and schistosomiasis. Despite being a major component of human cells’ RNA (97 percent), lncRNAs were previously overlooked due to their lack of known functions. However, emerging evidence from cancer research suggests their potential in disease development.

“We found that lncRNAs play a critical role in maintaining homeostasis in the parasite that causes schistosomiasis, making them attractive targets for therapeutic interventions,” said Murilo Sena Amaral, co-corresponding author of the study and researcher at the Butantan Institute’s Cell Cycle Laboratory.

To achieve this breakthrough, the researchers analyzed data from public repositories. S. Manzoni It was more or less expressed when male and female worms were mated or separated. Based on the results, they selected three lncRNAs as candidate therapeutic targets.

The researchers first conducted In vitro Pairs of male-female worms are exposed to double-stranded RNA molecules capable of targeting specific lncRNAs. This treatment led to parasite sequestration, reduced viability, and inhibition of egg release, ultimately resulting in their death.

Next, the team tested infected mice S. Manzoni By injecting the same double-stranded RNA into the animals’ bloodstream, they successfully reduced the target lncRNA in the parasites, leading to their death and reduced viability of their eggs.

Schistosomiasis is classified as a neglected tropical disease and for more than 40 years, the only drug available to treat it is praziquantel. However, the drug has its limitations, including reports of resistant worms, highlighting the urgent need for alternative treatment options. The researchers’ study offers hope for a new drug that silences the expression of lncRNAs in the parasite and effectively eliminates them from the host’s bloodstream.

The discovery marks an important step forward in schistosomiasis research and holds the promise of a novel therapeutic approach to combating this debilitating disease. With further research and development, this ground-breaking study could lead to improved treatments that will change the lives of millions of people affected by schistosomiasis worldwide.

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