Gene therapy in Cystic Fibrosis

An understanding of basic genetics is essential to understand genetics and gene therapy.

Every cell in the body (except red blood cells) contains a complete set of genes. These genes contain all the information necessary to build a human body.

There are approximately 30,000 genes located on each chromosome. A human cell has 23 pairs of chromosomes, with one chromosome in each pair from each parent.

The CF gene is found on chromosome 7. A child that has CF has inherited two faulty genes, one from each parent.

Genes are segments of DNA that hold the recipe for making a specific molecule, usually a protein. Proteins are the building blocks of the human body.

In 1989 an international team of scientists identified the CF gene on chromosome 7. They found that it makes a protein called CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), which transports salt and water in and out of the cells that line the lungs and digestive system.

CFTR doesn't function properly in CF. Usually, it gives out too much salt and too little water, which is why sticky mucus clogs the lungs and there is extra salt in the sweat

The identification and isolation of the CF gene in meant that scientists could find ways of correcting the basic CF genetic defect rather than just treating the symptoms of the condition. The best way to do this is through gene therapy - replacing faulty genes with normal ones.

As lung damage is the major cause of illness and death in CF, the first attempts at gene therapy are focusing on delivering genes to the lungs.

UK based researchers have already demonstrated correction of the genetic defect in mice, the human CF nose and, most recently, in the human CF lung. The next step is to try to develop effective treatment for people with CF.

This won't be an easy process. Gene therapy is still in its infancy, and there are many problems to overcome.

The Cystic Fibrosis Trust has brought together the UK's leading CF geneticists to form the UK CF Gene Therapy Consortium. The scientists are based in Edinburgh, London and Oxford.

The Cystic Fibrosis Trust pledged to raise the necessary funds to carry out this work and through the support of the CF community, we have so far invested well over £15 million in this project.

The £15 million has allowed the UK CF Gene Therapy Consortium to develop a lead product comprising the healthy (non-CF) DNA, a carrier to get the gene to the lungs and a promoter to tell the body to turn it on. Further tests for safety and efficiency are being carried out before a single dose trial planned for early 2008 and full multi-dose trials following the results of the single dose pilot study.

It costs around £3.5 million each year to fund the Consortium and it is estimated that the clinical trials will cost at least an additional £6.5 million. The exact amount will depend on the results of the single dose pilot study in early 2008.

For further information on the work of the UK CF Gene Therapy Consortium, please visit www.cfgenetherapy.org.uk