Therapeutics/Drugs

Coenie Louw from the Gateway Health Institute in South Africa will develop an oil-based suspension of the antibiotic amoxicillin, which is commonly used to treat pneumonia in children. Amoxicillin is normally reconstituted with water, but it can then only be stored for two weeks. A ready-packed oil-based formula would increase stability up to two years without the need for refrigeration, and also reduce the risk of contamination. He will mix amoxicillin with different types of oils and test their stability under different environmental conditions, and their viscosity for oral dosing.

Sangwei Lu from University of California, Berkeley in the U.S. will combine peanut butter with the antibiotic amoxicillin as a way to both treat pneumonia and boost nutrition in children from developing countries. They will test different formulations in healthy volunteers for texture and taste, and analyze stability over 12 months at different temperatures. They will also test the formulations for activity in a mouse model of pneumonia. The aim is to produce an inexpensive and ready-to-use medicine suitable for developing countries.

Rinti Banerjee of IIT Bombay in India will develop skin patches for safer and more effective dosing of the antibiotic amoxicillin in children with pneumonia in developing countries. Amoxicillin is usually provided as a tablet or powder that requires multiple doses per day, which, along with the bitter taste, is off-putting for children. They will develop amoxicillin-enclosed lipid nanoparticles that mimic the outer surface of the skin, and optimize their size and ability to encapsulate the drug.

Chenjie Xu of Nanyang Technological University in Singapore will develop a stable and child-friendly formulation of the antibiotic amoxicillin, which is used to treat pneumonia, for use in developing countries. Amoxicillin is unstable in water, and for oral delivery requires on-site mixing with sterile water, which is not always available. They will first encapsulate amoxicillin in microparticles, which become soluble only when exposed to an acidic environment such as in the stomach. The microparticles also help increase the concentration of amoxicillin and mask its unpleasant taste.

Haiqing Sheng and collaborators Carolyn Bohach and Scott Minnich from the University of Idaho in the U.S. will exploit the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) system in a dual approach to combat enteropathogenic Escherichia coli (EPEC) infections. EPEC cause diarrhea and result in several hundred thousand infant deaths annually.

Lori Holtz of Washington University in the U.S. will analyze the composition of bacteriophage (viruses that infect bacteria) in the gut of young children to see if it is linked with the chronic inflammatory gut condition, environmental enteropathy, which is highly prevalent in low-income countries and is linked to malnutrition and stunted growth. They will perform metagenomic sequencing on available fecal samples taken over a 6-month period from 489 children under age two from Malawi who were tested for gut dysfunction.

Jason Gill of Texas A&M AgriLife Research in the U.S. will develop an animal model for environmental enteropathy, which is a chronic inflammatory condition of the gut prevalent in children from low-income countries, to test new bacteriophage-based treatments. Bacteriophage (phage) are viruses that infect and can kill bacteria, and can therefore be used to treat bacterial diseases. They will develop a chronic disease model by infecting weaned piglets with low doses of enterotoxigenic Escherichia coli, which is likely involved in environmental enteropathy development in humans.

Paul Barrow of the University of Nottingham in the United Kingdom will identify bacteriophage (viruses that infect bacteria) that can reduce the presence of multiple pathogenic bacteria in the gut to restore healthy bacterial populations (microbiome) and help treat diarrheal diseases. They will characterize phage specificity for three major pathogens that infect both humans and pigs, and select those that are less likely to cause the development of resistance.

David Wang of Washington University in St. Louis in the U.S. will evaluate specific RNA bacteriophage (viruses that infect bacteria) as therapeutics to modulate the bacterial communities in inflammatory conditions such as environmental enteropathy. To date, only DNA phage have been explored as therapeutics despite RNA phage being able to kill a broader range of bacteria. They will test the effect of two prototypical RNA phage on the gut microbe population in a mouse model of intestinal inflammation.

Babak Javid of Tsinghua University School of Medicine in China will determine whether drugs that increase the accuracy of protein production in Mycobacterium tuberculosis, which causes TB, can boost the effect of existing TB drugs and thereby shorten the current 6 month treatment period. They hypothesized that resistance to TB drugs is caused in part by the ability of the bacterium to change its proteins by making random errors during their synthesis (known as mistranslation).