Cystic Fibrosis Research: What is This Trouble-Making Protein?

It only takes one little mutation to cause a whole host of problems!

While my pharmacology and drug development class has been intriguing, so far I think we are really starting to get into the good stuff now.  We are starting to get into the thought process behind how to develop a drug.  A very simplified view of the big picture: you pick a disease, gather research associated with that disease, pick a target for your drug to attack, learn as much as you can about that target, pick compounds to test against that target, screen the compounds for potency, efficacy and safety, do clinical trials and market your new drug.

Yesterday, we briefly discussed a few diseases and talked through a few of those steps with respect to the disease of choice.  Some of the topics brought up were rheumatoid arthritis, cancer, alzheimer’s disease (AD), and cystic fibrosis (CF).  These were all interesting for a variety of reasons.  When a drug company wants to design a new drug to put on the market for a particular disease, there are certain things that company should take into consideration: Does this disease affect a lot of people?  What is the severity of the disease? Are there medications already out there for this disease?  How much is this disease costing the society (via medicaid/ medicare)? At what level are we going to target the disease and are we going to be treating the symptoms or root cause?

The disease I found most interesting from our discussion was cystic fibrosis.  When I was younger, I was a dancer at a local ballet studio.  A wonderful instructor I had for a few years had CF. I remember her having to take breaks intermittently to cough, sometimes for several minutes. Her cough was one of the most horrible coughs I’ve ever heard.  I honestly don’t know how she was able to function as the beautiful active dancer with that terrible hacking cough.  Since then, I’ve learned quite a bit more about CF and how it affects almost every organ system in the body and causes countless problems at every level—all because of one tiny mutated protein.

According to the American Lung Association, approximately 30,000 Americans have CF, and there are over 1,000 new cases diagnosed each year.  The birth prevalence of CF in the US is 1 in 3,700.  It is caused by a mutated protein called Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is either not present in the cell membrane where it should be, or the protein is folded up in a way where it can’t perform its normal function.

The really exciting thing about CF is that a lot of information is available from the human genome project that researchers are using to work on a cure.  Because there are several different classes of mutations for CFTR, different groups are working on trying to fix or find work-arounds for each class.  This is especially exciting for me because my teacher has survived for many more years than is common for CF. I would love to see a cure come about for her to continue living a full life and continue dancing.

Here are a few photos showing the effects of cystic fibrosis and the mutated protein that causes CF: