With each issue, Trib+Health brings you an interview with experts on issues related to health care. Here is this week's subject:
Margaret Phillips is a professor of pharmacology at UT Southwestern Medical Center. Her research has focused on malaria treatments, among other topics. That work has included a collaboration to find a potential single-dose for malaria, an effort that has been documented in a five-minute film produced by the Medicines for Malaria Venture. Click here to view the film.
Editor's note: This interview has been edited for length and clarity.
Trib+Health: You’ve researched malaria and malaria drugs. Could you summarize what your most recent research has been about?
Margaret Phillips: Malaria is not a disease that we in the U.S. think about a lot unless we’re traveling to tropical areas, but it’s one of the most important infectious diseases globally. Fifty percent of the world’s population is still at risk for malaria, and there’s still almost a million people, about 0.6 million people in the latest report, that die every year of malaria.
And that’s mostly children under the age of 5 living in Africa who are at greatest risk. Of course, any of your readers in the United States who travel to these endemic areas could potentially acquire malaria, and they would be at risk for some of the more severe complications.
The real issue here, though, for malaria, is that even though we’ve had a lot of drugs over the years, the parasite is very good at becoming resistant to drugs. Right now, the drug that’s used for the frontline treatment in places like Africa is showing signs of resistance.
There’s a really big concern that we’re going to lose this drug to drug resistance and that there then won’t be an effective therapy to treat patients, especially in these endemic areas. That will lead to large increases in the number of deaths over what we’re seeing right now. That would obviously be very tragic.
There are no really great vaccines, only ones with sort of partial efficacy, so the need for new drugs to be there if we lose these current ones is really, really important and key. We have this really strong need for drug discovery. My own research has been one where we started at a very basic science level to identify compounds that could be used for drug discovery, and then we brought this all the way forward to the point that we’re actually in clinical development.
Drug discovery in this type of area is a different task than drug discovery in some of the more dominant clinical diseases that we have in the U.S., like a cancer or heart disease. It’s traditionally been sort of difficult for major pharma to completely be immersed in drug discovery for these types of diseases because of the market and things like that. What’s really arisen in the last 15 years are these partnerships between funders like Bill and Melinda Gates and NIH and industry and academia to try to move forward on malaria drug discovery.
One of the biggest drivers in this area is this not-for-profit organization called Medicines for Malaria Venture, which is based in Geneva. We’ve worked very closely with them in our program and once we had discovered a compound that was potentially good enough for clinical development they’ve basically taken on its clinical development.
What’s very important is that through these partnerships there’s been a really robust pipeline now of malaria drugs, future drugs that are being worked on. Hopefully from this we’re going to have something available when the current drugs are no longer effective.
Trib+Health: What got you interested in studying malaria and drug resistance?
Phillips: I come from a background of biochemistry and being interested in the enzymes themselves and how they work. My entire career I worked on parasites, so I was already interested in that area. But I really became interested in malaria in particular because of the great need, and I have always had this interest in drug discovery. As an academia person, it’s been a little bit hard in the past to get too far in drug discovery. We could work in the early stages, but it was always difficult to get the kind of chemical programs you need going to really make progress.
What really changed things, like here, at UT Southwestern, where our biochemistry department actually built … a facility where you have a library of possible chemical starting points that allows you to screen through that library and find ones that might have activity for your particular disease. We used that approach to find the initial starting points for this drug discovery program. Then we worked collaboratively [with other labs] to actually perform this drug discovery from this initial starting point, also with our collaboration with Medicines for Malaria Venture.
What you have to do is you take that initial starting point and you have to optimize it so it will potently kill the parasites, but also so it works in vivo. So when a patient takes it, the drug will actually enter the bloodstream and be there in high enough concentrations to actually kill the parasite.