With a three-year, $420,000 award from the National Institutes of Health (NIH), a team of researchers at Worcester Polytechnic Institute (WPI) will test a plant-based therapy it is developing that may prove to be a highly effective and low-cost treatment for malaria, one of the world's most prevalent and deadly infectious diseases.
According to the World Health Organization, more than 200 million people contracted malaria in 2012 and some 627,000—mostly children under the age of 5—died from the disease. Caused by a mosquito-borne parasite, the illness is reported in nearly 100 countries and threatens nearly half of the world's population.
Led by Pamela Weathers, PhD, professor of biology and biotechnology, the WPI team is testing a therapy that consists of dried leaves from the sweet wormwood plant, Artemisia annua. The plant produces a compound called artemisinin, which in combination with other antimalarial drugs is the primary treatment for malaria today.
Unfortunately, artemisinin combination therapy (ACT) is expensive to produce and is often in short supply in areas hit hardest by the disease. In addition, while the combination therapy is designed to be less prone to the drug resistance that has rendered previous antimalarial agents ineffective, the malaria parasite is beginning to show signs of resistance to ACT, particularly in Southeast Asia. "Malaria remains a major global health crisis and the increasing drug resistance is alarming," Weathers said. "Our ultimate goal is to make an easy-to-produce therapy available to the people who need it most."
Artemisia annua has been used as an herbal therapy for thousands of years, typically as a tea infusion to treat fever. Today, artemisinin, the principal therapeutic compound in the plant, is extracted, purified, and combined with other drugs to make ACT. Weathers's team takes a different approach, using dried whole leaves from Artemisia annua as a medication.
In previous work Weathers and her colleagues have shown that mice fed powered dried leaves had 40 times more artemisinin in their blood stream than mice fed pure artemisinin. Furthermore, the whole-plant therapy was five times more effective in clearing the disease-causing parasite from the mice. In addition to delivering more artemisinin to the bloodstream, the effectiveness of the whole plant treatment may be due to the presence of other potentially therapeutic compounds in the leaves.
In the new study, Weathers will use a laboratory model of the human digestive system to discover which compounds in the leaves move through the intestinal wall. She will focus on several compounds, including flavonoids and terpenes, which have exhibited antimalarial effects of their own and which may also help artemisinin move through the intestinal wall and into the bloodstream where it can attack the malaria parasite.
Flavonoids are widely distributed in plants and have various functions, including giving blossoms color. They are also believed to work synergistically with artemisinin to kill the malaria parasite. Terpenes are among the essential oils that play a role in the plant's defense system. Secreted terpenes have anti-microbial properties and deter some leaf-eating predators.
In a series of experiments over the next three years, the Weathers lab will use a cell culture model to study how the flavonoids and terpenes move through a layer of cultured human intestinal wall cells. They will also test the flavonoids and terpenes in combination with artemisinin to see how they affect the movement of artemisinin across the cell layer.
"Because these other compounds in the plant have some therapeutic activity, using the whole plant becomes an effective plant-based combination therapy," Weathers said. "Through this study, we hope to develop a better understanding of what compounds in the plant may be involved in making artemisinin more bioavailable."
While the NIH-funded project progresses, Weathers is also working with several groups in Africa and the United States to establish a new economic model for using whole plant therapy to combat malaria. She envisions local operations where farmers grow the high-producing cultivars of Artemisia that she and others have developed as a supplemental crop and deliver the leaves to processing stations, where they would be dried, pulverized, and homogenized, and where the powder would be placed in capsules or compacted into tablets for distribution to local populations.
"The beauty of all this is that the plant is easy to grow in most areas and the production process is relatively simple," Weathers said. "It could be an important boost for local economies and for the health of local populations."
