Molecules That Can Eliminate the Strongest Malaria Parasites Push Antimalarial Drugs Development
Wed, April 21, 2021

Molecules That Can Eliminate the Strongest Malaria Parasites Push Antimalarial Drugs Development

Scientists at the Institut Pasteur and French National Center for Scientific Research (CNRS) made a breakthrough that can push forward the development of drugs against malaria / Photo by: Alexander Raths via 123RF

 

Scientists at the Institut Pasteur and French National Center for Scientific Research (CNRS) made a breakthrough that can push forward the development of drugs against malaria.

In their study, the researchers identified molecules that can inhibit DNA methylation in which methyl groups are added to the DNA molecule and kill even the most resistant malaria-causing parasites.

The results of the study showed the importance of epigenetic DNA modifications for the parasite's life cycle, specifically in the strains of resistant parasites known as artemisinin. Findings are detailed in the journal ACS Central Science.

 

Progress for Antimalarial Drugs

Artemisinin is a drug-resistant strain of the Plasmodium falciparum parasite, which is transmitted to humans through bites from infected mosquitoes. Even though they are transferred from different hosts, the parasite can still result in adverse effects because the plasticity of their genome allows them to adapt to varied environments.

It is this plasticity that the scientists wanted to understand, specifically the DNA methylation. In doing so, the researchers allowed the Plasmodium falciparum parasites to interact with human red blood cells in a series of in vitro experiments.

After the parasites infected and developed in the blood cells, the investigators then tested more than 70 methylation-inhibiting molecules to determine the efficacy and their specificity associated with the parasites.

"As soon as we tested the first molecules, we saw significant activity, comparable with drugs such as chloroquine," Flore Nardella, a contract researcher from the Biology of Host-Parasite Interactions laboratory, said in a statement.

She noted that this activity was "very rare" during tests of a new library of molecules. CNRS Director of Research Paola B. Arimondo emphasized the efficacy of the inhibitor molecules that killed the Plasmodium falciparum parasites in the blood in just six hours.

Artemisinin is a drug-resistant strain of the Plasmodium falciparum parasite, which is transmitted to humans through bites from infected mosquitoes / Photo by: ababilhot via 123RF

 

The Most Effective Molecules

Another round of experiments was conducted in which the researchers tested the most effective molecules on resistant isolates. The results were, once again, conclusive: the inhibitor molecules successfully killed the blood parasites.

"This study shows, for the first time, that parasites in the blood, including artemisinin-resistant strains, can be killed rapidly by targeting DNA methylation," Arimondo explained.

Nardella echoed the statement, saying methylation can help develop new drugs that can be combined with artemisinin and eliminate resistant parasites.

Another series of experiments, which tested the inhibitors in vivo in mice infected with another parasite, Plasmodium berghei, showed similar results. The treatment once again proved its efficacy when it eliminated the blood parasites and the mice lived through the cerebral malaria infection.

The researchers are planning to continue their development on the selectivity and efficacy of the most effective molecules, so far, for antimalarial drugs. They will also keep an eye out for molecules that may heed similar results in other developmental stages of the parasites accountable for malaria transmissions.

The Global Burden

The results of the succeeding work are important, especially now that malaria continues to be a burden on global health. If the efficacy stands after additional research, the treatment can help address the issue of antimalarial drug resistance that has undermined the control efforts for the disease.

Malaria still affects millions of people worldwide. According to the World Health Organization, there were an estimated 219 million cases of malaria in 87 countries in 2017 out of which 435,000 resulted in death in the same year.

Africa holds the highest share of the global malaria burden, being home to 92% of the cases and 93% malaria-related deaths.

Nearly half of the world's population is still in danger of the life-threatening disease. Some population groups are at higher risk of catching and developing the severe disease. The most susceptible of all are children aged below five years old—the group that accounts for 61% (266,000) of all malaria deaths in 2017.

There are ways to prevent people from contracting the disease such as sleeping under insecticide-treated mosquito nets and indoor spraying with residual insecticides.

Only one vaccine is available for protection against malaria, which partially acts against the Plasmodium falciparum. Large-scale clinical trials have shown the vaccine—known as the RTS, S/AS01 (RTS,S)—can prevent about 4 in 10 cases of malaria for four years in children who received four doses.

The Fight Against Malaria

As of 2018, only nine countries were able to eliminate malaria while the rest of the world continues its bout against the mosquito-borne disease.

Based on the WHO Global Technical Strategy for Malaria, countries have 10 years to achieve global targets toward malaria control and elimination. By 2030, the world must have reduced malaria cases incidence by at least 90%, reduce malaria-related deaths by at least 90%, eliminate cases in at least 35 countries, and prevent a resurgence of the disease in all countries that are certified as malaria-free.

The world still has a long way to go, but developments in various areas in the fight against malaria are showing promising results. These developments, however, should be tied with new aggressive measures to further the progress against the disease.

As of 2018, only nine countries were able to eliminate malaria while the rest of the world continues its bout against the mosquito-borne disease / Photo by: kwangmoo via 123RF