Cystic Fibrosis Gene CTFR. What is it?

Hi all,

The past two postings have mentioned the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene.

Some mutations to the CFTR causes CF, and CFTR is indeed the primary cause of Cystic Fibrosis. To allow a better understanding of this important root of Cystic Fibrosis, today’s post focuses on this CF gene.

The CFTR gene was identified in 1989 by geneticist Lap-Chee Tsui and his research team. Everyone has two copies of this gene, one from each parent ( Children who inherit a faulty CFTR gene from each parent will have CF. However; those who inherit a faulty CFTR gene from one parent and a normal CFTR gene from the other parent usually have no symptoms of cystic fibrosis, as they will have enough normal copies of the gene to be healthy (

Breaking down the acronym CFTR provides a glimpse of how it operates. ( –

Cystic Fibrosis – the disease that occurs when two copies of the gene do not function properly
Transmembrane – the prefix “trans” means “across” , so transmembrane means across the membrane (CFTR is a transporter gene)
Conductance – the ease with which electricity, gas, or fluid flows through a substance
Regulator – a mechanism of control

To go into further detail about CFTR, it is part of a family of genes that regulate the energy transfer which enables a cell to open and close its ion channels, and is located on the human chromosome 7. The CFTR gene produces the CFTR protein, which regulates the chloride ion content of certain cells in the body. When chloride ions are not able to leave the cells properly, as is the case with CF patients, water is retained in the cells, and as a result, some fluids, including mucus, are thicker than they should be.

A functioning CFTR gene is critical to normal human development, and mutations to this gene are life threatening in most cases, because they compromise the function of the pancreas, gastrointestinal tract, and respiratory systems. When the respiratory system is compromised, mucus build-up in the lungs result in infections. As for the related dysfunction of the pancreas and gastrointestinal tract, the results are the likely destruction of the pancreatic exocrine function and lack of proper absorption of nutrients (

Live life.

Check out the YouTube video of this posting at

BTW – If you would like me to research and post any topic of interest regarding Cystic Fibrosis, please feel free to e-mail your suggestions to me at I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.


follow url Topic for the next posting – Early Study of CF Medication Formulation CTP-656 Shows Superior Effects Compared to Existing CF Medication Kalydeco

Cystic Fibrosis Gene Mutation DF508. What is it?

Hi all,

As many in the cystic fibrosis community are aware, the new, breakthrough CF medication Orkambi is only approved for those patients who have two copies of the cystic fibrosis gene mutation Delta F508 (Double DF508). But what really is this particular gene mutation? That is the topic of today’s posting.

There are over 1,500 mutations that have been identified on the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). According to the website, only approximately 20 mutations of those 1,500 mutations occur commonly in the Caucasian population ( DF508 is just one of those mutations, and is caused by a deletion of the three nucleotides that comprise the codon for phenylalanine (f) at position 508.

DF508 is the most frequently identified CF gene mutation throughout the world. As a point of reference, an estimate of those with CF who carry DF508 on a worldwide basis is said to be at 75% (

DF508 is a mutant CFTR protein which cannot be folded into its proper shape when produced. The quality control mechanisms within the cell destroy this abnormal protein before it can reach the cell surface where its major normal function is to act as a channel through which chloride ions can pass in and out of the cell ( On the other hand, a correctly formed CFTR protein opens channels in the cell membranes that releases chloride ions out of cells, which causes osmosis to draw water out of the cells (

In fact, part of the way that Orkambi works successfully is by one of its combinations assisting to move the defective CFTR protein to its proper place at the cell surface. As well, another combination of Orkambi increases the activity of that protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs and other organs (

Scientists have estimated that the DF508 mutation occurred over 52,000 years ago in Northern Europe. A hypothesis that supports the evolvement of this mutation is that it causes a positive effect by reducing water loss, since DF508 inherently does not allow the release of water from the cells, during cholera, which was a common cause of death in Europe when the mutation first appeared (

Please check out the introduction of this posting at Youtube at

NEXT POST to Our CF Matters Hawaii, September 26th – “Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). What is it?”


FDA Approves Cystic Fibrosis Medication ORKAMBI – July 2, 2015

Hi All,

On July 2, 2015, the FDA approved the break through Cystic Fibrosis drug Orkambi (  This CF drug, which is produced by Vertex Pharmaceuticals, together with an earlier developed CF medication, Kalydeco, are the first medications to try and counteract the underlying genetic defect that causes the disease, as opposed to only treating symptoms of this disease, as historic medications have done.

Approximately 30,000 Americans have CF, which is characterized by the buildup of sticky mucus in the lungs, causing frequent infections and a gradual decline in lung function.  Orkambi has been approved for those cystics who have two copies of the CF gene mutation F508del, of which about half of those 30,000 individuals hold these two mutations.   Of that subset, Orkambi has been approved for around 8,500 individuals aged 12 and older.

Orkambi’s approval was based on data from two double blinded, placebo controlled Phase 3 studies (TRAFFIC and TRANSPORT).  Results of those studies experienced statistically significant improvements in lung function, as well as decreases in pulmonary exacerbations (IV and/or hospital treatments) and improvements in Body Mass Index (BMI).

Orkambi combines lumacaftor and ivacaftor to treat these problems with a two-step approach. Lumacaftor helps move the defective CFTR protein to its proper place at the cell surface. Ivacaftor increases the activity of the protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs of people with Cystic Fibrosis ( ).

As stated above, at this point, Orkambi has been approved only for those CF patients with two copies of the F508del.  F508del is a deletion mutation on the cystic fibrosis transmembrane conductance regulator or CFTR protein which causes abnormal transport of sodium through membranes, leading to inflammation and mucus deposition in the lungs of patients ( /).

Orkambi is taken as a dose of two tablets every 12 hours (morning and evening) with fat-containing foods.

Please see the video introduction of this topic at YouTube –


NEXT POST to Our CF Matters Hawaii, September 19th – “Cystic Fibrosis gene mutation F508del.  What is it?”