June 2009

Connections - June09 - Basic Defect

Zeroing In on the Basic Defect: Attacking CF at Its Very Core

Imagine a pill that doesn’t just turn off the symptoms of cystic fibrosis — it attacks the disease at its very core. That’s what scientists and clinicians supported by the CF Foundation are now working to develop.

Twenty years ago, Foundation-sponsored researchers made a revolutionary breakthrough when they discovered the gene responsible for CF. By unlocking the genetic mystery of this disease, researchers realized they may be able to develop therapies that treat its underlying genetic cause, therapies that could control — or even cure — cystic fibrosis.

Today, Foundation investments in advanced therapeutics research are accelerating the development of a new type of therapy that treats the basic defect in CF, a faulty gene and its protein product.

The Problem in CF

Treating the basic defect in CF is like fixing a complex machine. “First, you have to understand what the machine does and what part of the machine is broken,” explains Philip Thomas, Ph.D., professor of physiology at the University of Texas Southwestern Medical Center in Dallas.

In healthy people, the CF gene makes a fully functional protein called CFTR. In cystic fibrosis, the CF gene is faulty so CFTR does not work properly. The faulty CFTR protein causes a salt imbalance, which leads to thick, sticky mucus buildup in the lungs and pancreas.

The Future of CF: New Technologies, New Solutions

Several of the Foundation’s biotech collaborators are exploring ways to restore function to the defective CFTR protein. Their work has led to the development of new therapies aimed at repairing, or modulating, the CFTR protein.

One of these therapies, VX-770, developed by Vertex Pharmaceuticals, Inc., showed promising results in clinical trials last year. “These drugs are absolutely for real,” said Dr. Susanna McColley, director of the Cystic Fibrosis Center at Children’s Memorial Hospital in Chicago, in a recent article from The New Yorker about efforts to cure CF. It’s striking, she said, that CF patients’ lung function improved while taking VX-770 during the trial, and then declined when they stopped the drug after the trial. She noted that experts never expected that patients with preexisting lung damage would see such drastic improvements when taking a drug like VX-770.

The Foundation believes compounds, like VX-770, that repair the CFTR protein are the most promising therapeutic avenue for treating CF.

Connections - June09 - Healthy Cell   Connections - June09 - CF Cell
Click image above to see how a
healthy cell functions.
  Click image above to see how a cell
with CF functions.

In the lungs of healthy individuals, cilia (fine, hair-like structures on cells) beat back and forth continuously in a thin watery layer to move mucus from deep within the lung toward the mouth. The thin, watery layer is created by the movement of chloride (a component of salt) out of airway cells, through protein channels. CFTR is embedded in the cell membrane at the cell’s surface in healthy people, forming the protein channel which enables chloride to move from within the cell to outside the cells.


In CF, the loss of function of the CFTR protein channel prevents chloride movement. Since chloride movement does not occur, the thin watery layer cannot form, the mucus layer grows larger, and the movement of mucus stops as the cilia are crushed and stop beating.

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