An international team of scientists lead by Professor Andrew Tobin at the University of Glasgow have discovered a new drug that not only kills the malaria parasite in the blood stream but also stops the disease from spreading.

It acts by disrupting the activity of a protein that is essential for the survival of the malaria parasite. This protein, called PfCLK3, is involved in a key biochemical process call protein phosphorylation. The activity of PfCLK3 also controls the production of other proteins that are involved in keeping the parasite alive. Blocking the activity of PfCLK3 therefore has a knock-on effect on a whole host of essential parasite proteins.

The malaria parasite has a complex life-cycle and exists in a number of different forms in our bodies. When the parasite is injected into human body through the bite of an infected mosquito it initially enters the liver. Here, it grows within the liver cells and divides into many thousands of parasites. These new parasites are then released into the blood stream where they invade our red blood cells. It is this stage of the disease that results in the symptoms of malaria which can result in the death of the infected person.

Anopheles mosquito

The next stage of the life-cycle is the development of male and female forms of the parasite. This happens to a small number of the parasites but is important because it is the male and female parasites, so-called gametocytes, which infect mosquitoes. When a mosquito bites an infected individual and takes up a blood meal, they also take up the male and female gametocytes. Within the gut of the mosquito the male gametocyte releases male gametes which then fertilise the female gametes, thus generating the next generation of parasites. These new parasites then migrate to the salivary gland of the mosquito where they can be released into the next person who is bitten by the infected mosquito.

Perhaps the most important finding of this new research is that inhibition of PfCLK3 can kill the parasite at all three stages of the life cycle – in the liver, in the red blood cells, and in in the male and female gametocytes. This means that the drug could potentially treat people with malaria relieving the symptoms, but also prevent transmission of the parasite.

Professor Tobin says “By killing the parasites at the various stages of parasite development we have not only discovered a potential cure for malaria but also a way of stopping the spread of malaria from person to person”.

Professor Andrew Waters, Director of the Wellcome Centre for Integrative Parasitology at Glasgow and a co-author of the study says “By inhibiting PfCLK3 we have shown that the production of proteins necessary for the survival of the parasite is stopped and this kills the parasite at multiple stages”

“In this way we have found a way to stop the transmission of the parasite by killing the form of the parasite that infects mosquitoes thereby preventing the parasite from being transferred from one person to another”

The study is a co-ordinated effort between the University of Glasgow and an international team of scientist including those at the drug company GlaxoSmithKline.

The study was funded by the University of Glasgow, Wellcome and the Medical Research Council.

 

First published: 30 August 2019

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