Thursday, December 29, 2005

Aussies Nail Malaria’s Tactics

From The Red Herring:

Scientists discover how the most deadly malaria parasite tricks the immune system.

Australian scientists have figured out how the world’s most deadly malaria parasite evades the immune system in a discovery that could lead to new treatments for the disease that kills an estimated 2.7 million people a year.

The findings were published online Wednesday in the journal Nature.

It turns out that the parasite, Plasmodium falciparum, is a master at deception, switching between different camouflage proteins as a fugitive might change jackets to evade the police. Like the police, human immune system cells cannot predict which camouflage the parasite will use next.

The parasite activates one camouflaged protein at a time, keeping the others inactive until the immune system recognizes that particular disguise and a new one is needed.

“It's like a leopard being able to change its spots,” said Alan Cowman, an international research scholar at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

“New forms come up, and the immune system beats them down again,” he added. “Because of this a lot of people think you need five years of constant exposure to malaria in its different disguises to gain immunity.”

Many children, who make up three quarters of the estimated 2.7 million people who die annually from malaria, do not live through the infection long enough to develop immunity.

Promoting Change
The researchers were able to explain how the parasite exercises such control over the camouflage proteins it expresses. It does this using a special region of DNA called a promoter.

“The promoter is all you need for activation and silencing,” said Dr. Cowman. “It's the main site of action where everything is happening. This is the first time anyone has actually been able to infiltrate an antigenic variation program.”

P. falciparum uses a protein to decorate the exterior of the red blood cells it invades. The protein causes the cells to adhere to the lining of the blood vessels, taking them out of the main circulation where the cells would likely be destroyed.

However white blood cells can still learn to identify the infected red blood cells and destroy them. Therefore the parasite has evolved a genetic mechanism which allows it to switch to a different protein.

New Therapies
The scientists say their new discovery could lead to new treatments which interfere with the parasite’s strategy of switching disguises.

Given the global toll of the disease, few would argue that pharmaceutical research into malaria has been disappointingly limited.

There is new hope, however. In late October, the Bill and Melinda Gates Foundation announced it would give $258.3 million for the development of a malaria vaccine, drugs, and research to combat the disease (see Gates’ $258M Grant for Malaria).

This is a significant step up from the $323-million total global funding in 2004 for malaria research and development. But critics would argue that still much more needs to be done. Researching and developing a drug all the way to approval frequently costs pharmaceutical companies more than $1 billion.

(Shamefully) Only two companies are listed by pharmaceutical industry organization PhRMA, as working on malaria treatments.

Hollis-Eden Pharmaceuticals, based in San Diego, California, says that mid-stage clinical trials of its drug Immunitin proved successful at reducing parasite count and cleared malarial parasites in most patients within a week.

Immtech International, based in Vernon Hills, Illinois, is also in mid-stage clinical trials for a drug called DB289.

2.7 million yearly deaths, only 2 companies doing any research. What a shame on humanity!

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