Understanding Cystic Fibrosis: From biology to diagnosis and treatment
- Deepti Kumar
- 17 hours ago
- 3 min read
Did you know cystic fibrosis was first discovered in the pancreas?
In 1938 Dr. Dorothy Anderson, an American pathologist coined the term “cystic fibrosis of the pancreas” based on autopsies of children dying of malnutrition, due to failure of the pancreas. The children in those days did not survive long enough to develop lung disease.
What is Cystic Fibrosis (CF)?
Cystic fibrosis is a genetic disorder caused by mutation in the gene that codes for the cystic fibrosis transmembrane regulator (CFTR) protein. Every individual has two copies of the CFTR gene. In order to have cystic fibrosis the person must inherit two copies of the mutated CFTR gene (one from the mother and one from the father).
The CFTR protein: What does it do? where is it present?
CFTR is a chloride channel that is present on the cell membrane and regulates the transport of salt and water across the cell in different tissues of the body including the lung, pancreas, skin, and sperm cells. In patients with cystic fibrosis the protein is either not functional or not made at all. This occurs due to mutations in the CFTR gene.
What happens if the CFTR protein is non-functional/absent?
The absence or lack of a functional CFTR protein results in dysregulation of the salt and water transport across the cells leading to thick mucus build up in the lungs, pancreas and excessively salty sweat. The thick mucus blocks the airways, and leads to frequent infections and inflammation ultimately damaging the lungs and causing respiratory failure and death. In the pancreas, it results in thick mucus around it and shows signs of scarring and cysts. Dehydration due to excessive loss of salt in sweat is another major concern for patients with CF. Other complications include infertility in men and difficulty for women to get pregnant.
Diagnosis
Early diagnosis of CF is important. It enables healthcare providers to start treatment and educate parents to keep their child healthy as much as possible. All babies in the US are screened for CF shortly after birth. This is performed by collecting blood sample from a heel pick. If the baby tests positive for CF then a sweat test is conducted to confirm the diagnosis. A sweat test is the gold standard for diagnosis of CF in children and adults. It measures the amount of salt present in the sweat. Diagnosis can also be performed as early as prenatally. The first step in prenatal screening is to test the mother for CF mutation through a blood test. If the mother carries a mutation in one of the CFTR genes, then the father is tested. If both parents are carriers then there is a 25% chance that the baby will have CF. Amniocenteses (done at 15-18 weeks of gestation) and chronic villus sampling (done earlier in pregnancy) can be performed to determine if the baby has CF. If the parents decide not to do these tests then the baby should be tested for CF at birth.
Hurdles in the path towards treatment
The discovery of the CFTR gene, the first ever disease-causing gene to be identified was a major milestone in human genetics and a breakthrough treatment seemed not so far.
However, discovery of over 2000 different CFTR mutations by geneticists to date posed an enormous challenge to development of transformative therapies for CF.
Moving past the challenges
CFTR modulator therapies have changed the face of CF, increasing the survival rates, decreasing the need for lung transplants, and improving the quality of life for patients with specific CFTR mutations. CFTR modulators are a class of drugs that are designed to correct the structure and function of the CFTR protein and are effective for only specific mutations.
What about the 6% of the people in the US with CF that have a combination of nonsense mutation and rare mutation and do not respond to modulators? Could gene therapy be the answer?
Gene therapy is gaining momentum and is being explored as a treatment option for this group. Gene therapy involves replacing the defective CFTR gene with the healthy copy of the gene in the cells. Currently gene therapy is being tested in clinical trials in the form of inhaler therapy for lungs in adults with CF.
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