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No gene therapy for Gauchers disease is currently being carried out in the UK but research on other diseases is taking place. At the Research Trust for Metabolic Diseases in Children's 13th annual conference held September 1994 in Stoke-on-Trent, two doctors spoke about their work on gene therapy to 300 members who attended. The two day Conference was a great success. Gauchers disease featured prominently being the first disease of its type to have a successful treatment (Ceredase). Professor Timothy Cox spoke about enzyme replacement therapy and its role in treating Gauchers disease. His speech is covered in his talk at the Gauchers Association's Conference.
Professor Bob Williamson of St Mary's Hospital, London spoke about gene therapy, which he has been researching since 1959, for the disease cystic fibrosis. He said there are around 4,000 genetic diseases of which 600-700 have had the genes isolated. For most recessive diseases (Gauchers disease is one), 90% of sufferers have no family history. Inherited diseases were rare.
Once the gene has been located and isolated, there is the opportunity to carry out genetic screening. 'We now have the opportunity to carry out screening for cystic fibrosis if people want it. This does not even require a blood sample - we can do screening analysis by using a mouthwash. made up from tap water.' He also said that prenatal diagnosis can be done on an egg taken from the mother before it is fertilised so only a healthy egg could be used for in vitro fertilization.
Professor Williamson said the idea of gene therapy was to put a copy of a normal gene into the body to replace the defective gene. This was called somatic gene therapy and did not change any inheritance pattern although he suggested that in 20 to 25 years time it might be ethical to correct an egg or sperm cell before conception which would affect future generations.
He dismissed criticisms of the ethics of somatic gene therapy. 'This is true low tech green medicine' he said. 'It should be possible to put genes into cells to prevent a disease appearing. It's much harder to reverse something which has gone wrong than to preserve normal function.'
The problem with gene therapy is to devise an efficient method for delivering the normal gene to the body so that it remains there and replaces the defective gene. The gene needs to get into the required cells. It is therefore necessary to target the cell, get into it and express the gene so it does what is required of it. In the treatment of cystic fibrosis he had found that using fat particles as an inhaler was safe but not efficient. Another method using an adenovirus had been found to cause side effects. The third method, taking bone marrow cells from the patient, modifying them and returning them to the blood stream using a retrovirus is the route at which research is now being directed. Another method which might be used would be to put a gene under the skin to trigger a reaction when required (eg to produce insulin for a diabetic when someone eats).
But Professor Williamson warned 'Gene therapy will not be a magic wand.' It may need to be used in conjunction with other forms of therapy and there are possible dangers which cannot necessarily be foreseen. Using a virus could cause disease and may be difficult to get rid of. It had potential to cause trouble. Professor Williamson stressed that safety was absolutely paramount.
Looking to the future, he said at the moment gene therapy was being applied to two diseases but that in the next five years, a number of other disorders, including Gauchers disease, will be treated with gene therapy and that in 20 to 30 years time, it will be a general treatment for many diseases.
Dr Gareth Morgan of Great Ormond Street Hospital, London spoke about the gene therapy he had given to a child suffering from ADA deficiency. He prefaced his talk by stating 'There is nothing special about genes. They can go wrong like any other part of the body.' He said that nine patients worldwide had received gene therapy for ADA deficiency (which like Gauchers disease is caused by an enzyme deficiency). The method was to take some bone marrow cells from the patient, separate the stem cells, stimulate and grow these in the laboratory for a day or so and then culture them with a retrovirus carrying the normal gene. A proportion of the cells had shown expression of the missing ADA enzyme. Four days later the cells were returned to the patient.
Unfortunately there was no improvement in his patient during the first three months. Six months after treatment there were no cells with the normal gene in the blood although there were some in the bone marrow. A year later they could find no normal genes in the bone marrow. (The patient is also being treated with PEG enzyme replacement therapy and remains well). Two other patients in Holland and France were given the same treatment with similar results.
On a positive note, none of the patients were any the worse for having the gene therapy although it seems that it has not yet worked for them. (A recent report indicates that successful ADA gene therapy has been carried out at the NIH in Washington.)
Dr Morgan described some of the criteria needed for gene therapy. There had to be:
Dr Morgan also described some of the problems. The modified gene:
Professor William Krivit of the Institute of Human Genetics, University of Minnesota spoke about bone marrow transplantation. He started by saying it was no longer necessary for bone marrow to be tested by a biopsy; it can be done with a blood sample using spectroscopy. He commented that the development of Ceredase means that bone marrow transplants are no longer desirable for Gaucher patients except possibly some Type 3 Gauchers patients. .
Source: Gauchers News February 1995
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