Saturday November 17, 2018
Home Science & Technology Scientists at...

Scientists at Massachusetts Institute of Technology and Harvard University Discover Malaria Achilles Heel

The experiments include seeing how well each of the 12 compounds works, for how long, and whether resistance develops with any of the promising agents

0
//
Infected mosquito. Image Source: Wikimedia Commons.
Republish
Reprint

September 10, 2016: Scientists appear to have discovered malaria Achilles heel, a weakness common to the multiple stages of malaria infection. In doing so, they have found a compound that cured mice of the disease.

Once it’s entered the body through the bite of an infected mosquito, the malaria parasite, P. falciparum, behaves as a unique organism as it goes through three phases during its life cycle. Experts say most treatments are aimed at only one stage or another. Over time, the parasite can become resistant to therapy, sometimes as quickly as within one year.

But researchers at the Broad Institute of Massachusetts Institute of Technology and Harvard University have identified a single protein target that appears to be the disease’s weakness, according to senior researcher Stuart Schreiber, a founding member of the biomedical institution.

Malaria Infection. Image Source: Wikimedia Commons.
Malaria Infection.
Image Source: Wikimedia Commons.

Malaria protein

“We did discover a novel protein that’s made by the parasite, that’s needed for all three phases of its life cycle, and a series of novel compounds that potently inhibit this protein,” he said. “And we could show in an infected animal that we could kill the parasite in all three phases.”

Schreiber and colleagues published their findings in the journal Nature.

After discovering the protein, researchers screened a unique library of 100,000 small molecules, from which they synthesized about a dozen compounds that they tested in infected mice. The molecules appear to stop the production of this protein in all of malaria’s life stages, effectively killing the disease.

The mice were disease-free for a month, a length of time considered to be a cure. When they tried to infect other mice with the blood of the treated rodents, the animals did not become infected with malaria.

The compound that scientists tested was a one-time oral treatment. Schreiber was quick to caution that what works in a mouse is not necessarily effective in humans. But he is hopeful.

“I am the eternal optimist,” he said. “On the other hand, I do know that what’s ahead is extremely challenging and full of unknowns that can only be addressed by marching forward and running the key experiments.”

The experiments include seeing how well each of the 12 compounds works, for how long, and whether resistance develops with any of the promising agents.

In theory, Schreiber said a drug that works in all three stages of malaria could be taken at any point in the disease cycle, as a treatment and even as a way to prevent the disease.

The researchers note that individuals can remain infectious even while undergoing treatment. So their infection can be spread to someone else through a mosquito bite.

Information about the anti-malaria compounds is being made freely available to other researchers through an online database. The library contains compounds designed and housed at the Broad Institute that are not usually found in the arsenals of pharmaceutical companies.

Follow NewsGram on Facebook

Malaria infects over 200 million people each year. Once it has infected a human host, the malaria parasite evolves through a number of unique stages, from initial blood infection to liver infiltration where the parasite matures and reenters the blood stream.

The parasite then goes on to infect and destroy red blood cells, releasing thousands of daughter parasites that invade other blood cells, continuing the cycle of reproduction and infection.

Follow NewsGram on Twitter

It is during this later blood stage when symptoms of malaria occur, including very high fever, overwhelming sweating, debilitating nausea and diarrhea. Over half a million people do not survive, mostly children in sub-Saharan Africa.

The research by Schreiber and colleagues was funded by the Bill and Melinda Gates Foundation. A Japanese drug company, Eisai, has shown an interest in helping to further develop the experimental malaria treatment. (IANS)

Click here for reuse options!
Copyright 2016 NewsGram

Next Story

An Experimental Vaccine to Treat Malaria

Scientists hope to get a better grasp on the system these vaccines employ, known as cellular immunity. Harnessing this system could help tackle hepatitis and HIV infection.

0
Vaccines
A doctor assists people looking for treatment for malaria at a health center in San Felix, Venezuela. VOA

After decades of disappointment in efforts to develop a malaria vaccine, researchers are starting to see promise in a new approach.

While most vaccines trigger the body’s defenses to produce antibodies against a disease-causing germ, the new approach recruits an entirely different branch of the immune system.

If it works, it could open up a new route to attack other diseases, including hepatitis and possibly HIV, the virus that causes AIDS.

Nearly 450,000 people die of malaria each year, according to the World Health Organization. The parasites that cause the disease are increasingly becoming drug-resistant.

One successful vaccine has been developed so far, but it prevented only about a third of cases in a clinical study.

Experts have decided that’s better than nothing. The vaccine is being piloted in Ghana, Kenya and Malawi.

Vaccine
Defensive cells killed liver cells that were infected with malaria parasites. (VOA)

New angle

Other scientists are trying a different angle of attack.

There are basically two ways to prevent germs from causing infections. “You either prevent them from getting into cells with antibodies, or you kill them inside the cells with T-cells,” said Stephen Hoffman, chief executive officer of Sanaria, a company working on one vaccine.

Most vaccines target the infection by building up antibodies. “If you need to kill them inside the cells with T-cells, we haven’t been overwhelmingly successful,” Hoffman said.

But Sanaria is one group seeing success by targeting malaria parasites inside infected liver cells, the first stop in the complex life cycle of the disease.

One key difference is how the vaccine is delivered. Hoffman’s group tried a typical route: injecting radiation-weakened parasites into patients’ skin or muscle. That didn’t work.

But it did work when injected directly into veins.

Vaccine
A public health worker takes a blood sample from a woman to be tested for malaria in Bo Rai district, Trat province, Thailand. VOA

The weakened parasites traveled to the liver, where they set off an immune reaction. Defensive cells killed liver cells that were infected with malaria parasites.

And the liver’s defenses were ready when faced with the real thing months later.

Most of that early work has been done in mice and macaques. When Hoffman and colleagues did something similar with a handful of human patients, most were protected against infection.

No waiting

Recruiting immune cells in the liver is especially effective because “we don’t need to wait until the immune system figures out that the parasite is in the liver and starts mounting an immune response, which can take days and sometimes weeks,” said Adrian Hill, director of the Jenner Institute at Oxford University.

“By then, the malaria’s gone. It only spends a week in the liver, and then it’s out in your blood causing disease.”

Vaccine
FILE – A worker of the Ministry of Public Health and Population fumigates in the street against mosquito breeding to prevent diseases such as malaria, dengue and Zika in Port-au-Prince, Haiti, Feb. 15, 2016. VOA

Hill’s group just published a study in the journal Science Translational Medicinein which immune cells in the liver were triggered by using a protein from the parasite, rather than the entire organism.

Scientists hope to get a better grasp on the system these vaccines employ, known as cellular immunity. Harnessing this system could help tackle hepatitis and HIV infection.

Also Read: Alcohol Kills More People Than AIDS, Violence Combines: WHO

Drugs can control HIV infection but can’t eliminate it from the body.

“If somebody could get cellular immunity to work really well for vaccination, that would be transformative for a whole range of diseases,” Hill said. “Not just for infectious diseases that we want to prevent, but ones that we want to treat and we can’t treat today.” (VOA)