Tribute to Grégory Lemarchal: what is cystic fibrosis?

Monday September 7, TF1 broadcast in prime time why i livea moving portrait of singer Grégory Lemarchal, who died in 2007 of cystic fibrosis.

If this was a partly fictionalized TV movie, cystic fibrosis is a very real genetic and hereditary disease, which affects an average of 1 newborn in 4,500, or around 200 children, each year.

What is cystic fibrosis?

Cystic fibrosis is a genetic and hereditary disease that affects the cells of various organs that secrete fluids or mucus, mainly the lungs, sinuses, pancreas and intestines, gradually altering their functioning. It is the most common fatal genetic disease in the Caucasian population, with the life expectancy of sufferers not exceeding 50 years.

Cystic fibrosis is characterized by an accumulation of mucus in the respiratory and digestive tracts. Mucus is a fluid made by the body to line, moisten and protect the walls of certain organs. In case of cystic fibrosis, it becomes thick and viscous which decreases its fluidity. This results in consequences essentially at the level of the bronchi and the digestive canals, the functioning of which is altered and which can become obstructed. The major consequences are expressed at the level of the lungs and the pancreas, the functioning of which is altered.

What is cystic fibrosis caused by?

The disease is due to a genetic mutation, that is to say an alteration of a defective gene on each chromosome of the pair of chromosomes 7. In the case of cystic fibrosis, it is the gene and the protein CFTR which is carried by chromosome 7. The acronym stands for “Cystic Fibrosis Transmembrane Conductance Regulator”. This makes it possible to encode the CFTR protein which is present in the cells of certain mucous membranes of the human body, in particular of the respiratory and digestive systems. Its role is to facilitate the passage of molecules between the interior and exterior of cells. For people with cystic fibrosis, this functioning is modified, which causes inflammation of the mucous membranes, and thickening of the mucus. The most common symptoms are the appearance of chronic obstructive pulmonary disease (COPD), respiratory or/and pancreatic insufficiency and various infections.

The transmission of cystic fibrosis is said to be autosomal recessive, which means that both parents must be carriers of the mutated gene on their chromosome 7 and that the anomaly has been transmitted at the same time by the father and the mother.

If only one of the two genes is mutated, the individual is not sick but called a “healthy carrier”. A child will therefore risk being affected if both parents are healthy carriers. In this case, with each pregnancy for this couple, there is a risk in four for the child to inherit the two mutated genes and therefore to develop the disease.

How is cystic fibrosis diagnosed?

Since 2002, a systematic screening test has been carried out at the 3^and day after the birth of each newborn.

In older patients, the main diagnostic test for cystic fibrosis is the “sweat test”, carried out when symptoms are suggestive of cystic fibrosis (stomach aches, diarrhea or recurrent bronchitis). It consists of measuring the amount of chlorine in sweat: if the concentration of chlorine is high, the test is positive. A genetic test is then carried out by blood test to search for the 30 most frequent mutations on the CFTR gene: there are more than 1200 and not all of them can be searched for. This is why a negative genetic test does not eliminate the diagnosis of cystic fibrosis.

What are the symptoms of cystic fibrosis?

The forms and severity of the disease vary from person to person. The signs of cystic fibrosis can therefore appear from birth or later.

In the newborn, there may be a delay in the expulsion of the first stools (the “meconium”) or even a blockage of the intestinal transit (“meconium ileus”), with a later resumption of weight.

Respiratory symptoms often begin in early childhood. These are most often persistent and repetitive coughing spells, with sometimes difficult and wheezing breathing (obstruction of the small bronchi). Recurrent bronchial or pulmonary infections can occur with different types of germs depending on age.

At the level of the digestive system, the pancreas is the most frequently affected organ, and digestion is then more difficult. This results in transit disorders with pasty, fetid and abundant stools, even fatty diarrhea (“steatorrhea”) and stomach aches. Added to this is undernutrition with multiple deficiencies, particularly in the vitamins that need fat to be absorbed (A, D, E and K), with weight or growth retardation that may appear shortly after birth.

How do you live with cystic fibrosis?

Cystic fibrosis is an incurable disease, which evolves inexorably, but progress in research in recent years has increased life expectancy: from 7 years in 1965, it is now estimated at 47 years.

Early management, regular monitoring and an appropriate lifestyle can significantly slow the progression of the disease. For example, it is strongly advised to practice a sports activity to slow down the decline in respiratory capacity and improve quality of life.

Where is the research?

To date, there is no curative treatment for cystic fibrosis, that is to say that it cannot currently be cured. Current treatments therefore aim to reduce symptoms. However, research is very active. It has two objectives: to improve the current treatments which act on the symptoms and to develop a curative treatment in order to be able to cure the disease.

Today, researchers rely heavily on protein therapy. Since 2019, two separate trials on a new molecule, elexacaftor have shown promising results. Combined with tezacaftor, a corrector which prevents the elimination of the CFTR protein, and with ivacaftor, a potentiator which activates the protein inside the cell, it could significantly improve respiratory function.