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New study may find a cure for malaria

Researchers at the Department of Biomedicine participate in an international research project that has now found a promising compound which could turn into an effective drug against malaria.

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Malaria and Medicine

Malaria is a disease that kills about half a million people each year, 80-90% of them are children. 500 million people are infected each year. The disease strikes poor countries hard – both, from a humanitarian and an economic perspective. Current malaria treatment is predominantly based on a drug called arteminisin. The researcher who discovered this compound was awarded the Nobel prize for medicine in 2015. Unfortunately, the drug is not as efficient as it used to be.

"We are witnessing the development of new ”superparasites” that are immune to our current drugs. If this development continues and we dont find new efficient antimalaria medicine, we may end up in the same situation as we were 10-15 years ago, when about a million people died each year", says Inari Kursula.

She is professor at the University of Bergen, and leads the Norwegian-Finnish team investigating the mechanism of a new candidate drug, compound 49c.

Very promising

"The parasites pass through several life-cycle stages inside their host organisms, and it is very important that an efficient malaria drug targets several different stages of this cycle", says Kursula.

The substance they are currently investigating targets three stages of the parasite life-cycle. It does that by blocking two so-called proteases (enzymes) of the parasite that are important for spreading the parasite within the host body. Specifically, 49c blocks parasite invasion into the host’s blood cells. Also, if you are already infected it traps the parasite inside these infected cells. Leaving the infected cells is crucial for the parasite, and it is also what causes the characteristic malaria symptoms. If the parasite cannot spread from cell to cell at the right time, then it cannot make you sick either.

The article describing this research is now published in the high-impact magazine ”Science”:

"The results are very promising and have already attracted attention of companies that develop antimalaria treatment", explains the scientist.

Studying the molecular details

The contribution of the UiB-researchers to this research has been to produce and study the two enzymes (plasmepsin IX and X) that are central for the development of the malaria parasite and are the direct targets of the compound 49c. They study the exact mechanisms of how 49c inhibits these enzymes in the laboratory. This work is crucial since, according to Inari, the compound at its current stage is poorly suited as an effective malaria treatment:

"It is such a big molecule that it has to be injected into the bloodsteam using a syringe. Malaria drugs need to be given orally, though, due to economic and hygienic reasons in the poor countries", Kursula explains.

By studying the enzymes and the mechanism of action of 49c in the lab, the UiB scientists can discover which parts of the compound are important for the inhibitory effect, and which are dispensable. By removing the less important parts, it may be feasibly to produce a drug that is small enough for oral administration.

"We dont have a drug yet, only a candidate. It usually takes between five and ten years of work from having a candidate to having an effective treatment drug. We are only at the beginning", clarifies the scientist.

The researchers also hope that the substance may not only work against malaria, but also as a universal drug against other diseases caused by parasites. An example is toxoplasmosis, which can give serious fetal damage to the baby if a mother is infected during pregnancy.

Link to article: http://science.sciencemag.org/content/358/6362/522