ORLANDO, Fla.--(BUSINESS WIRE)--It starts with a bite. You may not even notice until moments later when swatting away the mosquito and you begin to scratch at the resulting small welt on your skin. Aside from the annoyance of the itchy discomfort you would have no idea that at that moment one of the most insidious global infections had infiltrated your body. Over time you may present with incessant chills, an unrelenting fever, body aches, and nausea as the parasite proliferates. Maybe it’s a bad cold - or worse, the flu. When in reality, with each passing hour, a disease that has claimed up to 300 million lives in the last century is wreaking havoc on your body. In 2021 the World Health Organization reported 247 million cases of malaria - 619,000 of which resulted in loss of human life.
A team of dedicated researchers at the human-on-a-chip company Hesperos, Inc. have taken on the challenge to investigate new ways to combat this disease in collaboration with the Medicines for Malaria Venture (MMV). Through their efforts they developed a human-based model to study the disease pathology and therapeutic effects in a pre-clinical platform. The result was the fabrication of a Malaria-on-a-Chip model. This microfluidic platform connects human liver, spleen, and endothelium with recirculating human erythrocytes in a controlled, self-contained platform. This pumpless system utilizes gravity to oscillate the platform which allows for flow even for mixing of serum-free medium, making it a potentially useful and user-friendly tool for future commercial studies.
“People are always surprised when I tell them I research Malaria. ‘Isn’t that no longer a thing?’ Yet still hundreds of thousands lose their lives each year. The disease often devastates some of our most vulnerable groups - pregnant women and children. I’m glad to be working towards the fight to provide relief to these communities.”
-Jakob Rupar, Scientist Team Lead, Hesperos
The research article was published in Scientific Reports, a Nature journal: https://www.nature.com/articles/s41598-023-35694-4. This new approach to the evaluation of Plasmodium falciparum and anti-malarial therapeutics is executed in a realistic human model. The driving force behind Hesperos, Inc. is to engage the scientific community to investigate novel approaches to understanding diseases. Since 2015 they have contributed to the world of microphysiological systems by utilizing a variety of Human-on-a-Chip models. The scientific team behind the development of the new malaria platform seeks to reduce the use of humanized animals for these disease studies by offering a model to better understand parasite behavior and therapeutic outcomes as it pertains to humankind. Each year billions of dollars and animal lives are lost due to failure to translate successful pre-clinical animal studies to the human body. The potential of this work seeks to alleviate ethical, economical, and health burdens across the globe.
Two major contributors to this tenacious disease are recrudescence, or the return of parasite proliferation following treatment, as well as the rise of adaptable parasites that develop resistance to treatment. As such, two phenotypic malaria disease models were generated: a system susceptible to chloroquine treatment which was inoculated with the 3D7 strain of the parasite; another was infected with the W2 strain which has developed a resistance to chloroquine treatment. Researchers successfully cultivated both parasite strains in the platform, a promising first step in generating a phenotypic disease model. To demonstrate an effective proof-of-concept platform for therapeutic development, infected systems were treated with a single bolus dose of chloroquine in hopes that parasite infected blood levels, or parasitemia, would diminish and later recrudesce. When 3D7 infected systems were treated with a single dose of chloroquine a significant decrease in parasitemia was observed with recrudescence observed after five days. Conversely, when the resistant W2 systems were dosed with chloroquine, parasitemia levels were moderately decreased when compared to the 3D7 model.
“We are proud of our team for developing this first-of-its-kind platform. It is our hope that exploring new approaches to disease modeling helps to galvanize new treatments for this catastrophic disease.”
-James Hickman, Chief Scientist, Hesperos
The new Malaria-on-a-Chip model offers a promising approach to drug discovery using human-based models and paves the way for new drug development in collaboration with MMV. The team's findings could be a significant step forward in the fight against malaria.
