Nav: Home

New tool in fight against malaria

September 18, 2019

Redesigning molecules originally developed to treat the skin disease psoriasis could lead to an effective new drug against malaria, according to an international team of researchers. The team modified a class of molecules called pantothenamides to increase their stability in humans. The new compounds stop the malaria parasite from replicating in infected humans and from being transmitted to mosquitos, and are effective against malaria parasites resistant to currently available drugs. A paper describing this new class of modified pantothenamides appears online September 18, 2019, in the journal Science Translational Medicine.

Malaria is a major global health concern, with around 216 million cases and 400,000 deaths annually. The deadliest form of the disease is caused by the parasite Plasmodium falciparum, which is transmitted to humans from the bite of an infected Anopheles mosquito. Because many Plasmodium parasites have developed resistance to the most common drugs used against them, there is a pressing need for effective new treatment options.

"We have known for a long time that pantothenamides are extremely potent against the malaria parasite, but they become unstable within biological fluids because an enzyme clips them apart before they can act," said Manuel Llinás, professor of biochemistry and molecular biology and of chemistry at Penn State and an author of the paper. "Our team of collaborators, led by Koen Dechering at TropIQ Health Sciences and Joost Schalkwijk at Radboud University Medical Center in the Netherlands, found that changing a chemical bond in a pantothenamide molecule prevents this clipping, making it viable for use as a new antimalarial drug."

The team found that the modified pantothenamide molecules not only interfere with the development of the malaria parasite during its asexual growth phase in the blood but also prevent transmission of the sexual form of the parasite from human blood to mosquitos.

"By also preventing the transmission of malaria parasites from infected people into mosquitos, these pantothenamides can reduce the chances that mosquitos will be infectious to others," said Llinás. "It is currently widely accepted that next-generation antimalarial drugs must target the parasite at multiple stages to both cure the disease in an infected individual and prevent its spread to others."

Llinás and Erik Allman, postdoctoral scholar at Penn State at the time of the research, investigated exactly how the four most potent molecules in the compound class kill the malaria parasite. Specifically, they examined how these compounds affect the parasite's metabolism while growing in human blood.

The team discovered that, because the pantothenamide molecule closely resembles the essential vitamin B5, it is mistakenly taken in and metabolized by the parasite. This leads to the formation of molecular analogues, or antimetabolites, which decrease the parasite's production of acetyl-CoA, a compound critical for its survival.

"The molecule has a mechanism of action that hasn't been used before," said Dechering. "This means that there's no resistance to the drug as yet, and it is effective against many forms of malaria. Because parasite resistance to malaria drugs is a major problem worldwide, we are very close to a breakthrough."

"Pantothenamides have a simple chemistry, so they are easy and inexpensive to make," said Llinás, "And we now know their mode of action, which we don't always know before moving into drug development. This makes pantothenamides excellent candidates for further development and eventual clinical trials."
-end-
In addition to Penn State, Radboud University Medical Center, and TropIQ Health Sciences, the collaboration also includes researchers from St. Jude's Children's Research Hospital, Chiralix in the Netherlands, XenoGesis in the United Kingdom, the Swiss Tropical and Public Health Institite in Switzerland, the University of Basil in Switzerland, the Art of Discovery in Spain, Medicines for Malaria Venture in Switzerland, and Hermkens Pharma Consultancy in the Netherlands.

Penn State

Related Malaria Articles:

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the Umeå University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.
Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.
New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.
Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.
Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.
Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.
Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.
Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.
The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.
Free malaria tests coupled with diagnosis-dependent vouchers for over-the-counter malaria treatment
Coupling free diagnostic tests for malaria with discounts on artemisinin combination therapy (ACT) when malaria is diagnosed can improve the rational use of ACTs and boost testing rates, according to a cluster-randomized trial published this week in PLOS Medicine by Wendy Prudhomme O'Meara of Duke University, USA, and colleagues.
More Malaria News and Malaria Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#544 Prosperity Without Growth
The societies we live in are organised around growth, objects, and driving forward a constantly expanding economy as benchmarks of success and prosperity. But this growing consumption at all costs is at odds with our understanding of what our planet can support. How do we lower the environmental impact of economic activity? How do we redefine success and prosperity separate from GDP, which politicians and governments have focused on for decades? We speak with ecological economist Tim Jackson, Professor of Sustainable Development at the University of Surrey, Director of the Centre for the Understanding of Sustainable Propserity, and author of...
Now Playing: Radiolab

An Announcement from Radiolab