Chemical stops deadly diarrhoea
Molecular stopper could fight
cholera and mimic cystic fibrosis.
13 January 2003
|In some ways cystic fibrosis
is like the opposite of diarrhoea.
A newly discovered chemical could help to treat cholera and
other diarrhoeas. The compound may also aid the search for drugs
to treat cystic fibrosis.
The chemical stops cells losing their fluids. In secretory
diarrhoeas, the body pumps water into the intestine. In
developing countries, dehydration caused by diarrhoea kills more
than a million people each year.
Cystic fibrosis sufferers face the opposite problem - too
little secretion in the lungs, resulting in an ultimately deadly
build-up of mucus. This hereditary disease affects about 30,000
people in the United States.
A protein called CFTR controls secretion in both diseases.
Researchers have now found a chemical that stops it working1.
"We knew cystic fibrosis mice [lacking CFTR] don't get
cholera," says biophysicist Alan Verkman of the University of
California, San Francisco. "We thought that if we could block
CFTR, we could limit secretory diarrhoea."
Verkman and his colleagues tested 50,000 molecules for their
ability to stop CFTR working. They used human cell cultures, and
a yellow fluorescent dye that shows up secretion.
One compound reversibly blocked CFTR, was non-toxic to human
cells and mice, and reduced diarrhoea in mice with cholera by
The compound is a good candidate for treating cholera and
other bacterial infections, such as traveller's diarrhoea. "The
possibility that this could be used to treat disease is fairly
substantial," says cell biologist Qais Al-Awqati of Columbia
University in New York.
Oral rehydration therapy can treat diarrhoea. A salt and
glucose solution stimulates the intestine to absorb water. But
new treatments could help to prevent severe dehydration and
death in the young and old.
Cystic fibrosis patients lack CFTR. "Secretory diarrhoea is
like the opposite of cystic fibrosis," says Al-Awqati.
Verkman's discovery could aid the search for a cystic
fibrosis drug to activate or replace CFTR. The CFTR-blocker
could mimic the disease in pigs or rabbits, which have lungs
that are similar to those of humans.
"Mice don't truly reflect cystic fibrosis," says biochemist
Robert Beall, president of the Cystic Fibrosis Foundation in
Bethesda, Maryland. "We need an appropriate model with
human-like symptoms to screen drugs."