[Effects on Health] Scientists find way to cheaper malaria drug

from The Monterey Herald

By BETSY MASON
Contra Costa Times

BERKELEY - More than a million people die of malaria each year because treatment, about $2.40 per person, costs too much for most victims, largely children in Asia and Africa.

But a team of University of California Berkeley scientists believes they can cut the cost to 25 cents a dose by engineering a mass-producible version of the cure's key ingredient.

For the past two years, Berkeley bioengineer Jay Keasling has led an effort to engineer bacteria to make a form of the life-saving drug. The work has paid off and his team announced this week that they have overcome a major obstacle.

"This was a really critical step for us because it was the biggest hurdle to producing the drug in microbes," he said.

It may be five years or more before the work results in an affordable drug in the world marketplace, but Keasling is confident.

Malaria treatment has become more difficult in recent years because the parasite that causes malaria has become resistant to drugs such as quinine and chloroquine.

"At five to 10 cents per dose, chloroquine was cheap and effective for quite a while," said Mark Young, a senior health advisor at UNICEF. "But over the last decade, the resistance has been growing to the point that chloroquine is no longer effective."

Recent efforts have focused on preventing malaria by killing mosquitoes that carry the disease with nets treated with insecticide, as well as treatment. But the cost is prohibitive: More than $3 billion a year is needed for nets and drugs, said Young.

But that much funding is not forthcoming, and children are suffering the most. Nine out of 10 malaria deaths are among sub-Saharan African children below age 5.

"It's still a disease that's killing too many children, at least 3,000 every day and about a million every year," he said. "It's the biggest killer of children under 5 in Africa."

The good news is there is effective treatment available that works on resistant strains of the malaria parasite. And the parasites are not likely to become resistant to this drug because at the request of the World Health Organization, it is produced with various combinations of chemicals to keep the bugs guessing.

The problem is that the treatment is 10 times as expensive as chloroquine and out of reach for many victims. According to UNICEF, many African families spend a quarter of their income on malaria treatments.

The drug is costly because artemisinin, the key ingredient, can only be gotten from wormwood. Extracting it from the plant, or synthesizing it in the lab, are expensive processes. Getting the cost of the artemisinin-based combo drugs down to near what chloroquine used to cost would be extremely important, said Young. "That possibility is very much welcomed by the malaria community."

So Keasling's team has been retooling a microbe to help create the drug to avoid the costly lab synthesis.

Previously, they devised a way to insert yeast and plant genes into the E. coli bacteria to coerce it into producing a precursor to artemisinin.

Now, Keasling, along with botanist Dae-Kyun Ro and biochemist Eric Paradise, have taken another critical step closer by persuading yeast to turn the artemisinin precursor into artemisinic acid, which can be chemically synthesized into the drug.

"Now we are getting closer to reality," said Ro. He used the genomes of lettuce and sunflowers, which produce a compound similar to artemisinic acid to identify the enzymes involved in the production. He compared those genomes to the wormwood genome to find the corresponding enzyme that changes the precursor into artemisinic acid. The research appeared Thursday in the journal Nature.

Since yeast is genetically much closer to wormwood than the E. coli bacteria is, it was easier to coax the yeast into making the acid. But the team still hopes to one day use bacteria for the whole process because yeast takes two hours to double itself, and E. coli takes just 20 minutes.

"We need to engineer the enzyme to fit into the E. coli background," said Ro. "If you can save time you can reduce the cost. This is all about the price."

With the aid of $43 million from the Bill & Melinda Gates Foundation, Keasling's group has teamed up with the Institute for OneWorld Health in San Francisco and Amyris Biotechnologies in Emeryville, Calif., to streamline the synthesis and commercialization of the drug. They are one year into the five-year grant, and hope to have the process complete in the next four years.

"We obviously want it out there as soon as possible," said chemical engineer Neil Renninger, vice president of development at Amyris.

But Keasling stressed it is critical for farmers in Asia to keep growing wormwood so current supplies of the drug don't dry up or become even more expensive.