A review of Gene Therapy

a talk by Dr Richard Wade-Martins

(Wellcome Trust Centre)

Normally when the subject of gene therapy is raised in civilised conversation the topic invariably falls to cloning and genetic engineering. We enter a realm of post apocalyptic eras and science gone mad popularised by science fiction writers the world over.

Dr Wade-Martins stepped out in front of the tentative ears of the gathered conglomerate of Boys, Staff and Halley Society Committee members, fully expecting to hear of the science behind these wild tales, and the notion that in thirty years we will sit at home whilst a legion of clones perform our every whim, however Dr Wade-Martins was the bringer of a greater dream, a dream that he and others in his field have been striding towards for decades.

His field of research is the use of genetic manipulation to create a cure for a variety of diseases ranging from serious genetic diseases, such as cystic fibrosis to the common cold.

How hard can this be? You might think? It sounds so simple. In fact the difficulties are present right from the start, take cystic fibrosis an inherited (genetic) condition affecting the glands that produce mucus, tears, sweat, saliva and digestive juices. Normally, these secretions are thin and slippery, but in CF, mutations in the cystic fibrosis conductance regulator (CFTR) gene cause the protein made by CFTR, which controls the movement of salt and water into and out of cells, to become blocked, causing cells to produce the abnormally thick mucus characteristic of cystic fibrosis. Instead of acting as a lubricant, the secretions may plug up tubes, ducts and passageways, especially in the pancreas and lungs. Respiratory failure is the most dangerous consequence of CF.

Gene therapy offers great promise for life-saving treatment for CF patients since it targets the cause of CF rather than just treating symptoms. Gene therapy for CF had its start in 1990, when scientists successfully corrected faulty CFTR genes by adding normal copies of the gene to laboratory cell cultures. In 1993, the first experimental gene therapy treatment was given to a patient with CF. Dr Wade-Martins explained how researchers modified a common cold virus to act as a delivery vehicle - or "vector"- carrying the normal genes to the CFTR cells in the airways of the lung.

Subsequent studies have tested other methods of gene delivery, such as fat capsules, synthetic vectors, nose drops or drizzling cells down a flexible tube to CFTR cells lining the airways of lungs. Researchers are now testing aerosol delivery using nebulizers (a familiar device to any asthma sufferers).

But finding the best delivery system for transporting normal CFTR genes is only one problem that scientists must solve to develop an effective treatment for CF. Scientists must also determine the life span of affected lung cells, identify the "parent cells" that produce CFTR cells, find out how long treatment should last and how often it needs to be repeated.

The first cystic fibrosis gene therapy experiments have involved lung cells because these cells are readily accessible and because lung damage is the most common, life-threatening problem in CF patients. But scientists hope that the technologies being developed for lung cells will be adapted to treat other organs affected by CF.

This is just one of the many uses for gene therapy, which hopefully will lead to a better quality of life for all sufferers of all genetic diseases. 

The research being carried out by Dr Wade-Martins involves the use of Herpes Simplex virus as a vector for whole genes, including non-coding regulatory regions, and his initial results were explained to us and are looking hopeful.

For more information this web site provides an interactive flash presentation of the causes of CF

http://www.yourgenesyourhealth.org/cf/cause.htm

Tom Weedon