Rutgers scientists develop new drug to combat malaria

<p>A new drug entering clinical trials may be able to treat malaria by forcing the parasite to absorb excessive water, causing it to blow apart.</p>

A new drug entering clinical trials may be able to treat malaria by forcing the parasite to absorb excessive water, causing it to blow apart.

A new malaria drug created at Rutgers will soon undergo clinical trials for the chance to one day be used in treating the disease in poverty stricken areas of the world.

The drug candidate will be tested on humans, according to FDA normal procedures.

The drug is currently a candidate and is qualified to be tested on humans where it will be tested for safety, said Spencer Knapp, a professor in the Department of Chemistry and Chemical Biology, who helped prepare the drug.

"Every drug in the U.S. goes through a procedure to check for safety, efficacy and side reactions,” Knapp said.

Roughly 3.2 billion people throughout the world live in areas where they can be infected with malaria, according to the World Health Organization. Over the last 15 years, there were 37 percent fewer cases, and 60 percent fewer of infected patients died from the illness.

In 2015, there were 214 million cases. A little under 440,000 of these patients succumbed to the disease.

The various modifications and improvements were mostly conceived at Rutgers, Knapp said. Scientist in the lab would modify the molecules and try to improve it with the hopes that the properties would be more stable and soluble.

“The molecule they ended up with, SJ-733, was first made in quantity at Rutgers,” Knapp said. “About 80 grams of the drug was made at Rutgers.”

Most of the early compounds were active, but too insoluble to use, he said. It is essential for malaria drugs to be water soluble in order to offer it to individuals in the form of a pill.

Artemisinin Combination Therapies had been the previous go-to drug for malaria treatment, Knapp said, but recently resistance to Artemisinin has been discovered.

Better than something new is something with a new mechanism of action, he said.

“How it works is the drug candidate interferes with the sodium pump in the parasite and eventually results in the parasite exploding from taking in too much water,” Knapp said.

In essence, the malaria drug blows up the parasite.

It is also a new protein target, therefore the organism has not developed any resistance to it, he said.

If the drug passes clinical trials it is most likely to be used in African countries where the disease is widespread among poor countries.

“There’s an interesting aspect of malaria that is different from other diseases, and that is primarily the people who get malaria are poor people in poor countries,” Knapp said.

This drug most likely will not be used in the United States because malaria is not an issue here, he said. It will be used in Africa and maybe parts of Southeast Asia.

The project to create this new drug was founded between a friendship Knapp had with one of the originators of the study, David Floyd, who had developed a collaboration with Kip Guy from St. Jude Hospital. When Floyd retired he helped set up the project at Rutgers.

The initial funding for this project came from the Gates Foundation,  but once it came to Rutgers, it received funding from the National Institute of Health, Knapp said. 

“It took more than five years to develop this drug and was tested with hundreds of compounds,” Knapp said. “Sometimes drugs take thousands of compounds, but a five year period is not unusual."

The drug has gone through animal trials and has been tested on rats, mice and dogs.

“That is perfectly standard,” Knapp said. “You want to test it on three different species to see if there is any obvious problem with it before it goes to humans.”

The drug’s patent is owned by Rutgers, St. Jude Hospital, and Medicines for Malaria Venture (MMV).

“The only thing we do at Rutgers really is the medicinal chemistry,” Knapp said. “So we design the compounds, we make the compounds, but for biological evaluation we send them to St. Jude.”

The clinical trials, which are considered phase two for the drug candidate, may take up to two years and could be longer.

Phase three of the drug is phased out and comes up if the drug has questionable side effects that need to be further evaluated. If people develop unusual side reactions to the drug candidate during phase three it may result in a longer wait time.

“Suppose one in 100 people have an allergic reaction to the drug, well you don't want to just test 100 people, you want to test a larger group," Knapp said.

There are many malaria drugs being tested around the world and a list can be found at the MMV website, he said.

If the drug passes the clinical trials Knapp said he hopes a company like Eisai will pick it up to be marketed.

Eisai is a Japanese pharmaceutical company that funded part of the clinical trials, he said. If it passes the trials, Knapp hopes that they will get the rights to market the drug. If the drug ever turns a profit, Rutgers would get some return on the patent.

“It’s part of our academic mission to do good around the world and it is part of my academic ambition as a teacher to use chemistry as a way of educating young people, and part of that is by doing cutting edge research and making important contributions,” Knapp said.


Nick Huber is a School of Arts and Sciences junior majoring in journalism and media studies. He is a contributing writer for The Daily Targum. He can be found on Twitter @njhuber95Huber.

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