Australian researchers say they have found the key to a new anti-malarial drug, which kills the parasite with a salt overdose. It's the first discovery in the fight against malaria in 20 years.
Professor Kiaran Kirk and his team at the Australian National University worked with researchers from the United States and Singapore to discover the mechanism which makes the new drug work. He told DW that understanding this will enable researchers to track its long-term effectiveness and to detect whether the malaria parasite is able to develop resistance.
DW: What is a salt overdose and how does it work in terms of the malaria parasite?
Professor Kiaran Kirk: The work was actually done by a student, Natalie Spillman, who spent four years researching this. We started with some basic biology questions. We knew the parasite invaded red blood cells and grew inside the red blood cell, we knew the red blood cell is full of salt, and we just wondered how the parasite dealt with that. And what Natalie showed was that the parasite is actually very leaky. The salt comes pouring in, but then it has a very effective molecular pump that sends the salt out again. So, the parasite is pumping salt out all the time. We identified the particular protein which we thought was responsible, and finished this work about 18 months ago. And then almost the same week a paper came out from a consortium based in Singapore and the United States, and they had developed a new class of anti-malarial drug. They had discovered it. They knew that a particular protein played some sort of role, but they didn't know how the drug worked, they didn't know what the protein's role was. And as soon as we looked at the protein, we recognized it. It was our salt pump. So, we then got together with the groups from Singapore and the US, and they sent us their compound - their new anti-malarial drug - and sure enough, it was a very effective blocker of the salt pump. As soon as you added it to the parasite, within minutes, the parasite immediately filled up with salt. We realized we now understood how this new drug worked. The drug works by stopping the salt pump, the parasite fills up with salt, and it dies.
Building on research
That's a fantastic example of international collaboration, and it's the first discovery in two decades, about 20 years…
In terms of newness… the drug is actually in quite advanced clinical trials with Novartis. It's in Phase II clinical trials and they're treating patients who have malaria to see whether it works. And where the newness comes in is that [while] there are clinical trials going on all the time, this is the first genuinely new chemical structure that we've had - that kills malaria parasites and that has got into advanced clinical trials - for 20 years. Up until now, it tends to be combinations of old drugs combined in novel ways, or chemical modification of drugs that we've known for some time that have worked. But this is brand new. This has never been used before and this is why it's quite exciting, because it's a brand new way to kill parasites and we now know how it kills parasites.
But we have over the years seen malaria evolve and develop resistance to drugs. So, what are the chances of the malaria parasite, say, moving to another part of our blood circulation system - could it move away from the red blood cells and decide to sit somewhere else? Is that totally unrealistic, or what are the chances?
Look, I think that the parasite won't do that - the parasite and we have been together for many, many millions of years, and the parasite is very highly adapted to living inside our red blood cells. But you're quite right - what it can do - and what it has done, what it has always done - each time we've had a new malaria drug, either quickly or sometimes over a longer period, it has developed resistance. So, it stays inside the red blood cell - it's always going to be a red blood cell parasite - but it can change, it can mutate in ways that ultimately make it resistant to the drugs we use. And so far, history tells us, with just about every drug we've developed, the parasite has shown it's been able to become resistant. And that's the worry with any new anti-malarial drug. If this one goes through into the field, the next question will be: will the parasite become resistant. And that's why understanding the mechanism is a major advantage. Because if we know how the drug works, we can then look at the parasite, see if the drug continues to work, and whether the parasite is able to change its pump so that the compounds don't block it anymore. That's the sort of questions we can ask. It gives us an advantage. This won't eradicate malaria, but understanding this gives us an advantage in this constant "us against the parasite" - with its developing resistance and our developing new drugs.
And this would be relevant for malaria around the globe - there aren't types of malaria where this wouldn't be relevant?
Well, that's the hope. There are different types of malaria - humans get five different types of malaria. Plasmodium falciparum is the one that kills most people. [The drug] is currently being tested against that most virulent - the most deadly - of the parasites. All the indications are good that this will be effective very broadly, perhaps against the other types as well. So, the hope is that if it goes through the clinical trials successfully, it would be a drug that would apply throughout the tropical world - everywhere where there is malaria.
You mentioned that the drug is in Phase II clinical trials, but there is some way to go. So, in the meantime, would it be foolish for us - travelers to malaria prone regions - to consume more salt as prevention? Would that help?
No, that's not going to help - and I should perhaps clarify that. What is killing the parasite is the salt inside the red blood cells. All of our cells have salt in them. If you take extra salt, you'll just affect your blood pressure - it won't affect the amount of salt inside your cells, that's not how the body works. So, this is not a claim that table salt can cure malaria. It's playing with a very fine balance of salt control that the parasite has going on inside the blood cell. Consuming salt will not help you, and if you have high blood pressure, it'll hurt you. So, that's not something that you should consider as an anti-malarial strategy.
Professor Kiaran Kirk is the director of the Research School of Biology at the Australian National University (ANU) in Canberra.
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