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PATH receives grant to expand drug research for deadly diarrhea

June 16, 2014 by PATH

Partnerships will be key to eventual scale-up of innovations to reduce child deaths

Elena Pantjushenko, 650.392.2537,

Seattle, June 16, 2014–PATH announced today a three-year, US$15.6 million grant from the Bill & Melinda Gates Foundation to build a portfolio of projects with the goal of developing safe and effective treatments for severe acute secretory diarrhea (ASD). ASD, a type of diarrhea characterized by rapid onset and severe loss of water and electrolytes, causes most of the child deaths due to diarrheal disease around the world.

PATH will explore potential antisecretory drug targets in the gastrointestinal tract that are thought to play a critical role in fluid secretion, and identify existing compounds or new leads to be tested as antisecretory treatments. Such drugs will complement the use of oral rehydration therapy (ORT), the current standard of care.

"This new grant will enable PATH to expand innovation in drug development to save the lives of more children in low-income countries," said Steve Davis, PATH's president and chief executive officer. "The partnerships we create through this project will be crucial for eventually scaling up use of any new treatments we may develop for diarrheal disease."

Approximately 600,000 children die from diarrheal disease every year worldwide, and millions more suffer long-term consequences, such as increased susceptibility to other infectious diseases, slowed growth, and delayed mental development. ASD is often caused by infection with rotavirus or bacteria such as Vibrio cholera and enterotoxigenic E. coli.

"Diarrhea continues to kill hundreds of thousands partly because ORT does not reduce the severity or duration of diarrhea, and its effect is not readily seen by caregivers, who may not comply with treatment," said Hing Sham, PhD, who leads research and preclinical development at PATH's Drug Development program. "Supplementing ORT with an antisecretory drug would not only allow ORT to rehydrate patients more effectively, but also provide more rapid relief of symptoms, which would increase compliance by improving the perceived impact of the treatment."

The new effort will build on PATH's previous work to develop antisecretory drugs for infectious diarrhea. An investigational new drug that has already emerged from this effort–iOWH032–blocks the flow of chloride ions and thus the loss of water out of the gastrointestinal tract, reducing dehydration. This drug recently completed a pharmacokinetics trial in healthy Bangladeshi volunteers and in patients with acute cholera. The portfolio approach funded by the grant will maximize the likelihood of success in developing treatments for ASD of different causes.

A key component of the new work will be engaging with public- and private-sector partners. For example, PATH will collaborate with Saint Louis University's Center for World Health and Medicine to evaluate drug targets and compounds at various stages of development and identify at least two promising drug candidates for evaluation in clinical trials. The two groups have collaborated on drug discovery for pediatric diarrhea since 2011, and this project will build upon encouraging results that emerged from this partnership in 2013.

PATH will also partner with pharmaceutical companies to access needed resources, ranging from compounds and assays to intellectual property and scientific and technical know-how. These partnerships will help to ensure that drug candidates emerging from this work will have an opportunity to be tested in clinical trials and that any drugs found to be safe and effective will ultimately reach the target population to reduce illness and save lives.

About PATH's Drug Development program

PATH's Drug Development program works to develop and ensure availability and accessibility of safe and effective new medicines for diseases disproportionately affecting people in developing countries. For more information, please visit