Today, the life expectancy of CF patients has increased from five years in 1964 to about 31 years. The UK National Screening Committee now recommends that neonatal screening for CF is offered for all newborn babies throughout the UK. This simple blood test helps ensure that babies with CF are spotted at the earliest possible opportunity, allowing treatment to begin at the most appropriate time. This allowed them to test whether the normal CF gene could be used as a therapy in itself.
Identifying the CF gene also allowed MRC researchers in Edinburgh, led by David Porteous(now director of the University of Edinburgh Centre for Molecular Medicine and part of IGMM) and Julia Dorin(now an independent research scientist at the MRC HGU) to develop a mouse that mimicked many of the features of the disease.
In essence, this involved producing the cystic fibrosis gene in highly purified form using biotech industry production processes and mixing it with a synthetic polymer that condenses and protects the gene material into a complex that can pass across the outer cell surface and deliver the gene to the cell lining the lung where it is read off into the missing protein.
That proof-of-principle came in 1993 and was followed almost immediately by the first clinical studies of non-viral gene therapy with colleagues at Imperial College London in 1995 with a follow on study at the Western General Hospital in 1997, the first ever study of gene therapy in Scotland. These early studies indicated that the gene therapy could work in principle, but it was very inefficient and short lived. In a ambitious plan supported by the Cystic Fibrosis Trust, the Edinburgh group joined forces with their colleagues at Imperial College and another CF gene therapy group in Oxford to form the UK Cystic Fibrosis Consortium in 2001. Since then, they have been working jointly to improve upon the experimental gene therapy of the 1990's to come up with improvements that hold the prospect for a more effective and longer lasting treatment. The Consortium is poised to return to clinical studies which will be conducted in London and at the Wellcome Trust Clinical Research Facility at the Western General Hospital. As well as setting and solving many scientific challenges this team effort has highlighted many of the challenges to undertaking this "bench to bedside" translational research, putting the IGMM at the forefront of this important aspect of biomedical research.
We hope this story of success is one of many which result from the formation of IGMM. Already there are others in the pipeline. Specialists in breast cancer plan to work with bone experts in the hope of discovering why breast cancer patients often go on to develop bone cancer. Researchers working on Paget's disease, which can cause serious bone deformities, are planning a project with yeast geneticists, as both share an interest in a biochemical pathway which is found in yeast but compromised in patients with the disease.
An early example comes from research into Cystic Fibrosis (CF) which was carried out by IGMM scientists even before the institute was launched. Cystic Fibrosis (CF) is a genetic disorder which affects over 60,000 people worldwide, and there are 300 new cases in the UK each year. CF patients suffer from an excessive build up of thick mucus in the lungs and digestive tract, which develops into progressive lung disease and pancreatic enzyme deficiency. There is currently no cure.
It has been known for a long time that CF is a genetic disorder: a couple who both carry the defective gene has a one in four risk of having a child with CF. It is also known that a protein called CFTR is responsible for CF. Around 1,000 mutations in the CFTR gene have already been identified, although not all of these cause the disease.
Research into the genetic mutations which lead to CF began even before researchers were studying the disease - an example of scientific serendipity! In 1986, MRC-funded researchers in Dundee published work describing a class of proteins found in bacteria which are involved in the transport of molecules across the cell membrane. This discovery became very important and relevant to CF because one of these proteins, called CFTR, was already known to be responsible for CF by controlling the stickiness of mucus, which is a key symptom of CF.
Meanwhile, MRC researchers led by Veronica van Heyningen at the Human Genetics Unit (then the MRC Clinical and Population Cytogenetics Unit and now part of IGMM) were looking for genetic markers for CF, with the aim of finding the gene that causes the condition. In the course of their research, they discovered another protein, called the CF antigen, which, although not the underlying cause of the disease, was very interesting because it accumulates in CF patients as a result of inflammation. Since then, this protein has been found to be important in the study of other inflammatory diseases, and even in tumours.
L1989, the gene for CF itself was finally identified by a consortium of US and Canadian researchers. The identification of the CF gene gave David Brock, an MRC-funded researcher at the University of Edinburgh, the tools he needed to work on ways to test for the condition and to identify individuals who were carriers, by genetically screening for the mutant gene. Pregnancy screening programmes were subsequently developed and implemented in the United States in the early 1980s.