New malaria drug "reverses" resistance

[Monad]

This sounds an extremely cool discovery:

http://news.bbc.co.uk/1/hi/health/7987459.stm

The drug contains a chemical which prevents the malaria parasite getting rid of a toxic by-product of feeding on red blood cells.

It also disables a genetic defence that prevents the existing drugs chloroquine and quinine working, Nature reports.

Cheap to make too

[DMB]

It's a pity that the estimated delivery date for the drug is ten years from now.

[Monad]

Yeah I don't really get that - it sounds like they have already established it's safe and easy to produce. I know they still need trials but 10 years? Is it a problem getting the drug companies on board because it's too cheap?

[4321lynx]

That news item is not very clear and badly punctuated but

It targets the way mosquitoes digest haemoglobin in red blood cells, from which they take amino acids as their food.

A substance called haem, a by-product of this process, is toxic to the malaria parasites, carried by mosquitoes, so they have to convert it into a pigment called haemozoin.

This drug prevents that conversion taking place, meaning the toxic pigment remains.


As I understand it:

The Haem molecule appears in the mosquito stomachwhen Haemoglobin is broken up.

Therefore the parasites affected by it are those remaining in, or taken in by, the mosquito, the ones (if any)transmitted to the human during that particular feed will be unaffected as they come from the insect's salivary glands & have no contact with stomach contents. The ones still carried by the mosquito will be killed by the haem, so at the next feed no parasite transmission will take place. This may or may not be correct.

But any parasites taken in with the human blood at that original feed would be destroyed.

Whether both above are true or if either of them is true it is malaria transmission that is "cured" ie prevented, with no curative action on the human "patient".

The great hope as far as treatment of malaria in humans is concerned is the drug's ability to reverse resistance to Chloroquine & quinine, either of which can then be used for treatment.


But a drug like this, if safe, would be the answer to the problem of malaria.

Note that it is deemed safe in animals (mice). No human studies have been done yet.

[ofro]

I strongly suspect that the article contains a big misunderstanding.

The digestion of hemoglobin in the insect's stomach in of no relevance here. Rather it is the use of the hemoglobin by Plasmodium, the malarial parasite in the human body.

Once the parasite has invaded a human red blood cell after being introduced into the human via the insect's saliva, it lives off the surrounding hemoglobin as source of amino acids. The digestion by product is heme, which is toxic to the plasmodium. It protects itself by converting the water-soluble heme into water-insoluble hemozoin crystals. It is this process that is blocked by the commonly used chloroquine. Perhaps the acridone mentioned in the article does the same, but I can't tell.

Now, acridone-based alkaloids have been known for many years (just Google "acrodine malaria"), so I don't know what is so special about this article. An acridone derivative is an effective antiviral drug, but who knows if it helps with malaria. I suspect that the estimated ten years of development time includes extensive screening of related compounds with the highest effectiveness and least toxicity, followed by testing in humans. I wouldn't be surprised if that isn't already done in the industry.

[4321lynx]

I strongly suspect that the article contains a big misunderstanding.

The digestion of hemoglobin in the insect's stomach in of no relevance here. Rather it is the use of the hemoglobin by Plasmodium, the malarial parasite in the human body.

Once the parasite has invaded a human red blood cell after being introduced into the human via the insect's saliva, it lives off the surrounding hemoglobin as source of amino acids. The digestion by product is heme, which is toxic to the plasmodium. It protects itself by converting the water-soluble heme into water-insoluble hemozoin crystals. It is this process that is blocked by the commonly used chloroquine. Perhaps the acridone mentioned in the article does the same, but I can't tell.

Now, acridone-based alkaloids have been known for many years (just Google "acrodine malaria"), so I don't know what is so special about this article. An acridone derivative is an effective antiviral drug, but who knows if it helps with malaria. I suspect that the estimated ten years of development time includes extensive screening of related compounds with the highest effectiveness and least toxicity, followed by testing in humans. I wouldn't be surprised if that isn't already done in the industry.

That sounds good. I think you've nailed it.