Finding and Opening Doors

The Goat Races were this weekend. Unfortunately Curly didn't win the whole thing, but he did win the first heat he ran in. My parents collected $280 in random donations for the CFF at the event, and hopefully were able to raise a fair amount of awareness for CF. 


Big news this week for the CF world! An email popped up in my inbox titled "Phase 2 Study of Kalydeco and VX-809 in Combination Shows Promising Interim Results". Hooray for VX-809! This is the drug that works on the DeltaF508 mutation.  It was shown to improve lung function as much as 10% in some patients! This is the kind of drug that is going to cure CF.


In discussions I've had with some friends recently, I think people have a hard time sometimes understanding exactly what the problem is with CF in relatively simple terms. I found this on Johns Hopkins CF website and thought it explains it pretty well. Its a little lengthy but read it through:

Sweat is produced in glands under the skin, transported to the skin surface through ducts, where some of the salt and water are reabsorbed. In normal skin functioning, as sweat moves along the duct most of the sodium and chloride -- the components of salt -- are reabsorbed. This is driven by a large force drawing sodium into cells lining the sweat duct. The chloride flows through the CFTR channel, while sodium flows into the cell through epithelial sodium (Na) channels (ENaC) in the apical membrane. 

The salt reabsorption process is markedly abnormal in people with CF. Chloride transport is virtually eliminated because CFTR, which is the main way for chloride to enter the apical, or top, surface of cells is defective. Chloride must travel through the CFTR, located on the surface of the duct cells, at the same rate as sodium to maintain a balance of electrical charges. This results in very little sodium and chloride reabsorption, leading to a high salt content in CF sweat -- so high that the sweat chloride concentration is the most reliable single test for CF.

The lung’s airways are covered with a thin, moist film called airway surface liquid, or ASL, a salt-containing liquid and a mucus gel layer. The ASL traps bacteria and foreign particles, while cilia on the surface of airway cells constantly move the particles out of the lungs and toward the mouth. This process, called mucociliary clearance, or MCC, is an important defense mechanism that protects the lungs from infection. ASL also contains antiproteases, antioxidants, antibodies and other substances that work together to neutralize or destroy invading organisms without damaging the lungs. In CF airways, decreased chloride transport is coupled with excess sodium transport out of the surface liquid. Since water follows the flow of sodium, the ASL loses volume and the mucus gel layer becomes dehydrated.

The Johns Hopkins website is so awesome to check out, with pictures and video's explaining how things work why they do with CF. Check it out if you have some free time - http://www.hopkinscf.org/main/whatiscf/index.html 


There are thousands of different mutations of genes that can cause CF. Drew has one called  ΔF508 and another called R560T. Mutations are grouped into classes based on the exact problem with the mutated cells. Click here for a little bit about the problems the different mutations cause. ΔF508 is a class 2 mutation. I, having no clue how cells work, rely on the analogies given by certain medical professionals to understand things. They often refer to the processing problem of a CF cell as a locked door and the sodium chloride either can get to the door but cannot open the door (class 3 problem) to get to the right place or it not being able to find the door in the first place (class 2 problem). You may recall several months ago the HUGE CF world news that a drug was developed that corrects the problem of class 3 mutations. When people take this drug, the problem of the broken CFTR gene not being able to open the door when it gets to the door is corrected. The data that was just released yesterday announcing promising results for the combo drug study uses that drug that came out in January in combination with a drug that leads the broken CFTR gene to the door, thus Class 2 mutations can both find and then open the door to get to the right place. I know its all a little confusing. If you EVER have the chance to hear Dr. JP Clancy speak anywhere, go. He is a brilliant man, and he is amazing and dumbing it down to a non-medical level (the door analogy). Its really pretty cool stuff, all thats happening in the CF world right now. I have so much hope for a different future!