The UK Cystic Fibrosis Gene Therapy Consortium: What is CF?

What is Cystic Fibrosis?

Introduction

Cystic fibrosis (CF) is characterised by abnormal epithelial ion transport in the apical membrane of most secretory cells. This leads to altered epithelial mucus secretion in the gastrointestinal tract, reproductive tract, liver, pancreas and most severely in the pulmonary epithelium.

Sweat glands produce excessively salty secretions, the pancreas is damaged, 10-15 % of neonates suffer from severe intestinal blockage termed Meconium ileus (MI) and thick mucus secretions build up in the lungs leading to respiratory infectionsand lung damage.

Current therapies include antibiotic treatments, pancreatic enzyme supplements, high fat diets, physiotherapy and heart-lung transplants. The continued development of conventional therapies particularly with reference to dietary control has greatly improved both the quality of life and the mean life expectancy of people with CF (Gaskin, 1988). In the 1930s for example, children born with CF usually died within a year of birth. Today though, the average life expectancy is between 30 and 40 years.

However, there is still no treatment for the underlying defect causing the disease and individuals with the disease suffer from a high therapeutic burden and a severely compromised quality of life.

How common is Cystic Fibrosis?

The prevalence of CF varies with ethnicity (Heim, R. A. et al., 2001), and is highest among people of North European decent (Boat, et al., 1989), with around 7,500 CF patients, and an incidence of one in 2,500 live births (Dodge, J. A. et al., 2007) in the UK.

The number of asymptomatic (Welsh, M. J. & Smith, A. E., 1995) heterozygous carriers of mutated CFTR gene is approximately one in 25, which equates to around 2.3 million people in the UK (http://www.cftrust.org.uk).

How is CF diagnosed?

Cystic Fibrosis is most commonly diagnosed by a sweat test, which is a relatively simple test whereby the skin is stimulated to produce sweat. This sweat is then analysed. Children who have cystic fibrosis have excessively salty sweat.

Following a positive sweat test, blood is usually taken for genetic analysis. This will usually involve looking for the common mutations, which will diagnose up to 85% of patients.

If the patient has a less common mutation, it may not be possible to easily identify it.