Researchers at the University of Nebraska Medical Center College of Pharmacy are collaborating with researchers from Monash University in Australia, the Swiss Tropical Institute and Hoffmann-LaRoche in Switzerland, to develop a new anti-malarial drug discovered at UNMC. The team will share a two-year, $3.3 million grant provided by Medicines for Malaria Venture (MMV), a unique, worldwide venture to develop new anti-malarial drugs.
In the 1840s, malaria was a major cause of 600 deaths among Mormons living in Omaha’s Florence area. In 1914, an estimated 600,000 cases of malaria occurred in the United States. Today, malaria is rare in the U.S. due to urbanization, improved sanitation, housing, nutrition and living standards, as well as eradication of mosquitoes with chemicals beginning in the 1940s.
Though now the malaria epidemic seems like a world away, in countries like Africa, Asia, Central and South America, the disease kills more than 1 million people each year, most of them children and pregnant women, according to the World Health Organization (WHO). In addition, an estimated 300 to 500 million new cases of malaria are diagnosed each year. More than 90 percent of all malaria cases occur in sub-Saharan Africa, according to the WHO.
In addition to the epidemic in Africa, the U.S. Centers for Disease Control and Prevention says malaria could reemerge in the U.S. due to the malaria parasite building up resistance to current drugs, environmental changes and increased air travel. American travelers and military personnel who travel to countries where malaria is prevalent are at risk.
Jonathan Vennerstrom, Ph.D., associate professor of pharmaceutical sciences and principal investigator of the grant, and Yuxiang Dong, Ph.D., post-doctoral research associate, are conducting the research at UNMC. They say MMV is unique because it brings together the private pharmaceutical industry and the public sector expertise in malaria research at institutions such as UNMC.
The team has developed a unique class of compounds that shows effectiveness against the parasite that causes malaria in humans. The hope is the compounds can be used to develop economical malaria drugs.
UNMC’s role in the venture is to make the compounds, purify them and work with other team members who test the safety and potential of the compounds. If successful, the next step will be clinical trials to test for effectiveness in humans by researchers in Africa and Southeast Asia.
MMV, an international public and privately funded organization, was formed in 1999 to create a unique way for developing new anti-malarial drugs that may otherwise not be developed due to cost. Initial co-sponsors of venture are the WHO, the International Federation of Pharmaceutical Manufacturers Associations, the World Bank, the Government of the Netherlands, the UK Department for International Development, the Swiss Agency for Development and Cooperation, the Global Forum for Health Research, the Rockefeller Foundation and the global Roll Back Malaria Partnership.
The UNMC team has identified several anti-malarial compounds in a new class of chemical structures. Its work has been called “spectacular” by the WHO. The team also has applied for a patent on the compound.
“We think we have something quite promising. Within the last two years, we’ve shown our compounds are remarkably effective in animal models,” said Dr. Vennerstrom, who’s been studying malaria for 15 years. He became aware of the disease while growing up in Ethiopia while his parents taught at mission schools. Malaria kills more people than any other infectious disease, with the exception of tuberculosis,” said Dr. Vennerstrom who from the age of seven until he was 16 years old, remembers taking antimalarial drugs to avoid getting malaria. He and his parents, who are missionaries, lived for nine years in Addis Ababa, the highlands of Ethiopia. “Having had experience growing up where malaria is a health threat gives you a perspective and interest.”
The disease, which takes an enormous toll in lives, medical costs and lost labor, is caused by a parasite that is transmitted by the bite of an infected Anopheles mosquito. The mosquitoes bite at nighttime, from dusk to dawn. The way drugs are typically brought to the market is through research and development at private pharmaceutical companies. Because a large percentage of drug development projects do not succeed, and because malaria drugs offer minimal return on investment, drug research and development must come in part from the public sector. That’s why MMV was established.
Dr. Dong, who was recently recruited, brings his chemistry expertise to UNMC. He received a doctoral degree from Karlsruhe University in Germany, one of the oldest and most revered technical education institutions in Germany. “Fortunately, my solid training in chemistry is useful in Omaha and beyond,” he said.
“It’s unique to combine his wonderful chemistry expertise to come up with potential new drugs to treat malaria,” Dr. Vennerstrom said. “One thing we think about all the time is how the compounds work—how do they exert their activity to kill malaria parasite. There are many things to consider when designing a drug.”
UNMC is the only public health science center in the state. Its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through its commitment to research, education, outreach and patient care, UNMC has established itself as one of the country’s leading centers for research in cancer, genetics, cardiovascular diseases, neurodegenerative diseases and arthritis. Over the past two years, UNMC’s research funding from external sources increased by 41 percent and now exceeds $43.6 million annually. In that same period, federal funding increased by 33 percent and now exceeds $26 million annually.