PATH announced today they received a grant from Japan’s Global Health Innovative Technology (GHIT) Fund to develop a new oral treatment option for soil-transmitted helminth (STH) infections. PATH’s Vaccine and Pharmaceutical Formulation team, part of the Medical Devices and Health Technologies global program, will lead the international collaboration, which includes the University of Massachusetts Medical School (UMMS) in the United States and Kao Corporation in Japan.

Necator americanus
Necator americanus (hookworm)

Soil-transmitted helminths are parasitic worms, such as hookworm, roundworm, and whipworm. STH infections can deprive the body of blood and nutrients, disproportionately affecting populations living in poverty primarily due to morbidity associated with malnutrition and anemia. Severe anemia in pregnancy is a significant contributor to maternal mortality. STH infections can be prevented and treated with benzimidazole. Yet, according to the World Health Organization, approximately 1.5 billion people are infected with this neglected tropical disease worldwide.

Current mass drug administration (MDA) campaigns for prevention in endemic locations are limited by three primary biological factors: reduced efficacy against Trichuris (whipworm), possible emergence of drug resistance, and restricted use of benzimidazole for pregnant women–in addition to logistical and financial constraints.

Blood flukes in Black and White

The PATH-led multisector team will focus on optimizing the antiparasitic protein Cry5B (a naturally occurring protein from the soil bacterium Bacillus thuringiensis), with the aim of producing an inexpensive, broad-spectrum Cry5B product suitable for use by adults, children, and pregnant women as an alternative to, or in combination with, existing benzimidazoles used in anthelmintic MDA campaigns. Studies have shown that Cry5B has promising potential to treat hookworm and roundworm, and have demonstrated strong activity against Trichuris in vitro.

An estimated 20 to 60 Cry variants will be produced by Kao Corporation in their Bacillus-based expression system, and then tested in vitro and in vivo at UMMS. Based on these study results, an enhanced Cry sequence will be selected for large-scale production for further development, toward the goal of helping to expand the reach of anthelmintic MDA campaigns and reduce the global burden of STH infections. Therapeutic Cry5B protein will need to be delivered via potent and unique formulations for pediatric administration and that protect the oral drug from degradation during transit to the gastrointestinal tract, where the parasitic worms reside.

This work will build on PATH’s previous GHIT Fund-supported drug development project, which focused on development of an appropriate Cry5B protein as a new therapeutic option for STH management.