Researchers have known for years
that one chemical that can 't exit cells because of the mutation in cystic
fibrosis patients' CFTR is chloride. This resulted in the widespread use
of the term "chloride channel" to describe the pathway that CFTR is supposed
to form. Much former and current cystic fibrosis research looks at the
question of why chloride's inability to exit cells causes the ill effects
of the disease.
That's where Hudson's approach diverges
from the status quo - her research holds that it is not chloride that is
primarily responsible, but that another chemical trapped by the malfunctioning
CFTR - glutathione - plays a crucial role. She noticed that the symptoms
of individuals with a known deficiency of glutathione outside their cells
are remarkably similar to the symptoms of cystic fibrosis patients. She
then identified a chemical mechanism that explains that effect.
In healthy people, the cells lining
the lungs, which are called epithelial cells, release glutathione onto
the lungs' surface, where it performs several important functions. As is
widely recognized by scientists, glutathione acts as an antioxidant that
neutralizes harmful oxidants in the air and those released by immune system
cells. The body also uses glutathione to break down mucus and make it thinner.
By the time they are in their teens,
cystic fibrosis patients have between 5 and 20 percent of the levels of
glutathione on the surface of their lungs that healthy people do. The defect
in their CFTR protein prevents the chemical from exiting their epithelial
cells. Therefore, the patient's lungs are more susceptible to damage from
oxidants and are plagued with thicker mucus than healthy people's are.
Those damaging effects fit easily into
Hudson's hypothesis, but extracellular glutathione deficiency at first
did not easily explain why cystic fibrosis patients are chronically inflamed,
even before becoming infected. Then she found research that showed that
certain immune system cells have another protein channel beside CFTR that
does allow glutathione to exit. She hypothesizes that, in a cystic fibrosis
patient's glutathione-starved lungs, the immune system cells emit a significant
amount of their glutathione in a futile attempt to make up the difference,
rendering them weak and ineffective. Low levels of glutathione in immune
system cells also signal inflammation.
That leaves patients suffering from
a vicious cycle - the lungs are chronically inflamed and laden with thick
mucus, which harbors infections. The immune system cells that are marshaled
to attack the infection are weakened and rendered less effective by a depletion
of glutathione. This leads the body to summon more immune system cells
that produce oxidants normally neutralized by glutathione but that instead
ravage the lung surface. The immune system also produces by-products that
build up, making the mucus even thicker.
Based on that biochemical mechanism,
Hudson's solution is simple - restore glutathione in the lungs to a healthy
level and halt the cycle.