Scientists Find a Way to Starve Malaria to Death

[Reported for one of the campus newspapers]

We have been losing the battle against the malaria at the rate of a million lives a year. Scientists now have found a novel way of attack that might turn the tide against this persistent disease.

An international team of researchers have unraveled the structure of digestive enzymes in malaria that would potentially lead to the creation of new drugs. The parasite has been increasingly getting resistant to traditional anti malarial drugs. Now a multidisciplinary team of researchers including McGill's own John Dalton have discovered the key enzymes that help the parasite to survive inside humans. These enzymes help the malaria to digest the proteins inside the human red blood cells, leading to the proliferation of the malaria and the destruction of the red blood cells. The new study have revealed the three dimensional structures of these enzymes thereby paving way for developing drugs that can attack these enzymes specifically. This way the malaria could literally be starved to death.

Professor John Dalton from the Institute of parasitology at McGill and his collaborators have just published their study in the Proceedings of National Academy of Sciences elucidating the structure of the enzyme. Dalton has been focusing on the malaria for fifteen years, and in the last year he and his collaborators announced the structure of the first enzyme in the same journal. Within a year the team has solved the mystery of second enzyme too.

Malaria has only one copy of each of these enzymes. Other parasites usually have several copies of similar enzymes, and if any of them is disabled they switch to another. But the researchers have shown that in Malaria, if either of the digestive enzymes is knocked out the parasite cannot survive. According to Dalton this is real breakthrough in the search for an effective anti- malarial drug. They also have demonstrated some of the specific drugs that can inhibit the function of these enzymes.

The development of the drug will have to go through various stages of testing and screening. Scientists believe that if everything goes well they will start trying them in humans as early as three to five years. They are aiming for a drug that could inhibit both enzymes at a time, or a combination of drugs that would target these enzymes separately which can be later combined in treatment. By attacking both vital enzymes at a time limits the ability of the parasite to develop resistance to the drug.

Researchers have been active in developing new classes of drug against malaria. A multidisciplinary approach was requires to tackle the problem. This was what Dr Dalton and collaborators were able to achieve. Dr. Dalton's collaborators came from various backgrounds with different types of expertise that helped them to take up this challenge together. Their team includes biologists studying the life cycle of malarial parasite, bioinformatic experts analyzing the malarial genome to pinpoint the exact enzymes, chemists to isolate these enzymes, and crystallographers to determine the structure of these enzymes. His collaborators are located in Australia, UK, Poland and McGill.

They have published the structures of these enzyme along with possible drugs in a public database, which other scientists can use independently to develop the drug. "Anyone who has experience with drug design would know how important is the structure of two potential targets. These structure will be in the public database. Also in last three months we have released a whole panel of potential compounds targeting these enzymes. They were also released to the public database. We have been very keen on giving everything to the public database. We did not want to hold them to ourselves." Dalton said.