February 8, 2017
Eisai and the Broad Institute (a joint research facility established by the Massachusetts Institute of Technology and Harvard University) are collaborating on a joint research project for the development of antimalarial medicines.
In September 2016, an article on the progress of this research was published in the world renowned scientific journal Nature. The article describes the identification of a group of candidate compounds with a novel mechanism of action which may lead to the development of new innovative antimalarial medicines.
New Drug Development: The Key to Malaria Eradication
Malaria is one of the three most prominent infectious diseases in the world. It is caused by Plasmodium parasites that are transmitted to humans through the bite of infected mosquitoes. According to the World Health Organization (WHO)1, malaria is still responsible for 500,000 deaths worldwide every year, most of which are African children.
Currently, artesunate-based therapies are widely used to treat malaria. In recent years, artesunate resistant forms of Plasmodium have emerged, and therefore development of new treatments has become a pressing need.
In addition, existing treatments have proven effective against Plasmodium after they've migrated to the blood and begun to reproduce inside the red blood cells, but are ineffective during the other stages of the disease (such as when the liver cells are infected). Therefore, new antimalarials that demonstrate efficacy throughout the entire life stage of Plasmodium are critical for eradication of the disease.
![[Mosquito Stages] 1. When an Anopheles mosquito bites someone. sporozoites are injected along with the saliva. [Human Stages] Human Liver Stages 2. Sporozoites infect human liver cells. 3. The number of sporozoites increases causing liver cells to rupture. Human Blood Stages 4. Sporozoites invade red blood cells. 5. Merozoites in blood can be verified by diagnoses. 6. Constantly altering their form within red blood cells, merozoites continue growing and multiplying. Some sporozoites are transformed into reproductive bodies that grow within a mosquite. [Mosquito Stages] 7. When an Anopheles mosquito bites someone infected with malaria, the merozoites within that person's blood are injected into the mosquito. 8. Zygote change their form inside a mosquito until they are able to infect someone.](/sustainability/atm/innovation/images/012_img_01.gif)
Unique Method of Creating Compounds leads to New drug Development
Drug discovery research generally starts with the screening of libraries consisting of a large number of compounds, using various methods to evaluate their efficacy. Typically, a compound library is created using small molecule compounds or natural substances. However, this project was initiated with the screening of Broad's Diversity Oriented Synthesis (DOS) compound library. The DOS library consists of various small molecule compounds that are similar in the part of natural substances. By screening a library inspired by natural substances yet rich in diversity, researchers are aiming to discover compounds with new mechanisms of actions that have not been addressed previously.
Over 100,000 compounds in the DOS library were tested, and a number of active compounds were identified with mechanisms that suggest efficacy at all life stages of Plasmodium. The results of the compound screening used in this research were made public at the Malaria Therapeutics Response Portal managed by the Broad Institute, and will hopefully assist the world's malaria researchers in their efforts to find new effective antimalarials.
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