Individuals with cystic fibrosis (CF) have persistent infection in the airways, which the
body attempts to fight by recruiting immune cells (neutrophils) to the lung. The immune
system and neutrophils are unable to completely kill the bacteria, and the response to the
infection leads to inflammation (swelling) of the airways and lung damage. Nitric oxide (NO)
has anti-bacterial and anti-inflammatory properties in the lung. NO production is decreased
in CF patients, and may contribute to the persistent infection and inflammation. Increasing
the production of NO in the airways of CF patients may help decrease this inflammation and
infection.
Rho GTPases are molecules in the cells that line the airways that decrease the protein that
makes nitric oxide (NOS). Rho proteins also increase inflammation in these cells. Rho
proteins are increased in CF cells, and may partially explain the low NO and high
inflammation seen in CF. Blocking the Rho protein in CF cells increases NOS, which can then
produce more NO. The Rho protein can be inhibited with a drug, simvastatin (Zocor®).
Simvastatin is used by millions of people to lower their cholesterol, is very safe, has few
side-effects and is approved for use in children greater than 10 years of age. We propose
that treating CF patients with simvastatin will increase NO produced (exhaled NO), and may
decrease airway inflammation.
If simvastatin has these expected effects in CF, it would be another drug that has potential
to become a new therapy to fight the debilitating lung damage of the disease.
Phase:
Phase 1
Details
Lead Sponsor:
Akron Children's Hospital
Collaborators:
Cystic Fibrosis Foundation Cystic Fibrosis Foundation Therapeutics