First UK Conference A Great Success

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The first conference of the Gauchers Association on 'Developments in Treatment of Gauchers Disease' opened to a packed hall of some 120 delegates on Sunday 22 November 1992 at the Clive Hotel Hampstead London NW3. Members, hospital doctors and GP's from all parts of the UK including Cornwall, Wales, Manchester, Sheffield, Nottingham, Swindon, Oxford, Cambridge and Cumbria as well as London and the home counties attended. There were also representatives from Holland, Germany, and the Republic of Ireland.

The conference was chaired by Jeremy Manuel, Chairman of the Gauchers Association, who in his opening remarks spoke of the remarkable progress of the Association since the founding meeting on 4 August 1991 attended by only eight people. "We now know of 100 sufferers of the disease" he said.

He then introduced Roger Barton MEP, Member of the European Parliament for Sheffield, Chesterfield & NE Derbyshire and a Patron of the Association. He said: ''My qualification is that I'm a carrier and I've given you another member''; he was referring to his son. He congratulated the Association on its successful first year and said that one of the reasons for this was the spirit of partnership between doctors, patients and the drug company. Referring to the potential for gene therapy, he added: ''This is a remarkable and exciting period when a complete cure may be on the horizon.'' He then declared the conference officially open.

Treatment of Gauchers Disease
Professor Tim Cox Consultant Physician, Addenbrooke's Hospital, Cambridge, said he has seen 30 patients with Gauchers disease and is currently involved in the treatment of 12 patients with Ceredase. He explained how the disease causes Gauchers cells to accumulate in the spleen, liver, bone marrow and bones and that these cells are normally digested by the enzyme which Gauchers' patients are deficient in. There are other diseases of this type, called lysosomal diseases, but Gauchers is the most common.

He said Gauchers is caused when two parents each have the recessive gene containing the defect. This meant that usually only brothers and sisters may get the disease. Their parents and children are mostly unaffected. Genetic testing can prove conclusively whether someone has the disease or not. He gave the example of a mother who has Gauchers. Her daughter suffered from nose bleeds so they thought the daughter might have Gauchers too. But genetic testing showed the daughter did not have Gauchers. So the nose bleeds had another cause.

Professor Cox summarised the various treatments available including spleen removal when the spleen became dangerously large, orthopaedic surgery such as hip replacement when bones deteriorated and even liver transplant which has been done in the US on three Gauchers patients. Bone marrow transplants have been used in very severely affected infants and children with Gauchers. He discussed whether spleen removal leads to increased bone involvement and gave the following figures based on 97 patients:

He said it cannot be claimed that spleen removal necessarily causes further bone deterioration. However he pointed out that spleen removal could lead to increased risk of infection and that patients should be immunised (with Pneumovax) against this, preferably before the spleen is removed; he also advises some such patients to take penicillin daily for life.

Enzyme replacement therapy is the best available treatment for most patients affected by Gauchers disease. It also offered the prospect of preventing the development of complications. He said that as far as we know it is safe and it works. He explained that research studies by his colleague Dr. Pram Mistry have indicated that the drug's lifetime within the target tissues can be measured over a few days rather than weeks, which would indicate that the ideal period between doses is two to three days.

Royal Free

Dr. Paul Fields, Senior House Officer in Haematology Royal Free Hospital, London NW3 spoke on behalf of Professor Victor Hoffbrand who was abroad. Prof. Hoffbrand, Consultant Haematologist, suggested the formation of the Association.

Dr. Fields reported results of two patients aged 11 and 16 who have been treated with Ceredase every two weeks for five months. They showed improvements in haemoglobin from 10.6 and 10.3 to 12.5 and 13.8 respectively. They also saw a fall in serum acid phosphatase levels from 58 to 25 and 26 to 14 respectively. (The level of serum acid phosphatase is raised in Gauchers patients and its fall can, in some cases, act as a guide to the response in treatment). A third patient aged 56 with severe bone involvement has been treated for two months with no change in haemoglobin and a fall in serum acid phosphatase from 38 to 30. There were no adverse effects.

The initial two infusions are made at the Royal Free after which they are given in the GP's surgery or by the GP at home. A Royal Free doctor is on call should the GP or patient wish to consult in the event of adverse effects.


Dr. David I K Evans, who has recently retired as Consultant Paediatric Haematologist, Royal Manchester Children's Hospital, explained that the severity of Gauchers disease varied enormously, with different symptoms even within the same family. He said splenectomy was no longer automatic for enlarged spleens but should not be ruled out.

Dr. Evans encouraged patients to seek out doctors who know about Gauchers disease and said the Association could help in this. ''The Health Service entitles you to a second opinion'' he said.

Dr. Evans spoke strongly against bone marrow transplants for Gauchers disease. ''Bone marrow transplants put you through hell. You have a 1 in 10 chance of dying and a 1 in 10 chance of complications. You need someone in the family who has the same tissue type. With a transplant from a donor panel there is only a 25% chance of success.'' He also added that patients with an enlarged spleen may have to have it removed before a bone marrow transplant.

The preferred treatment is with Ceredase. But not everybody responds in the same way to it. He encourages his patients to have treatment at home and said that almost everyone should be able to master the technique. His first two patients, both young girls, started treatment at 2.3 units 3 times a week. But after three months he changed the frequency to 7 units once a week because it was more convenient. After a year the dose is 15 units every two weeks.

In one case Katie, who was present at the conference, had responded very well; and photographs showed the extent of reduction in the size of her stomach (due to reduced spleen and liver size). In the other case the improvement had been slower and the dose has been raised.

Commenting on the use of Ceredase prophylactically, he said ''It seems to me sensible to start treatment in a child before all these complications set in.'' The dose will be smaller (and less costly) at a young age. And money does not need to be spent on 'debulking' if the bulking is prevented in the first place.

Patients Experience

Mr. Donald Tendell was the first adult to receive Ceredase in the UK. He told the conference: ''My life is transformed''. He said he had no side effects except that he started to feel better. Before treatment he had to give up work because of fatigue, was kept alive by blood transfusions and could not walk because one ankle collapsed. At the conference he looked a healthy person without any disease at all.

Ms Ruth Katz told the conference how lonely she had felt living with Gauchers disease before the formation of the Association and her treatment with Ceredase. Ruth was one of the original founding members of the Association and the second adult to be treated in the UK with Ceredase.

Before treatment she was recommended to have her spleen removed which she did not wish. ''After seven months on Ceredase the size of my spleen has been practically cut in half.'' Neither does she have to take huge doses of morphine any longer to gain respite from the intense, chronic pain from which she used to suffer. ''I can now look forward to a future without fear'' she said. She added that it took three to four months before she noticed any change in her condition from having the treatment.

Genetic Research

Dr. Ian Ellis of the Thames Regional Genetics Centre at Guy's Hospital, London talked about the work his Centre does in the field of genetic counselling and genetic screening. He said that genetic counselling provides information to patients who may be concerned about themselves and other members of their family. Genetic screening can be used:

However mass screening (which is not currently done) would raise the problem of discovering patients with no symptoms or very mild symptoms who do not want more medical involvement. One must ensure adequate counselling and understanding before testing in the wider population.

Mr. Andrew Walley MA of the Institute of Molecular Medicine, John Radcliffe Hospital, Oxford has just finished his first year of research into Gauchers Disease. His aim is to characterise the exact genetic defects which causes it. He described three different ways in which mutations could occur, all of which have been reported in Gauchers disease patients.

So far in his study of 26 non-Ashkenazi and non- Jewish patients he found approximately one third had the mutation N370S, one third L444P and about one third were as yet undefined (two cases being rare). He said it is known that 97% of Ashkenazi Jewish patients are accounted for by only four mutations. He also said the N370S mutation appears to pre-dispose patients to milder disease while the L444P mutation is associated with more severe disease.


Martin Cortvriend Area Manager UK/Ireland, Genzyme Biotherapeutics reported that 21 patients are being treated in the UK with Ceredase.

He explained the manufacturing process and quality control system to prevent infection which is extremely important as Ceredase is made from human placentas. He said because there were so few patients it was inevitably going to be very expensive .

He said he expected the placental version of Ceredase to become licensed in the UK in 1993 with the recombinant version possibly after 1994.

Payment for Ceredase is made in three different ways through the National Health Service:

  1. Patients are treated as ''extra-contractual referrals'': they go to a hospital outside their area which does not have an existing contract to supply services to their health authority.

  2. The District Health Authority agrees to provide extra money for treatment in one of its own hospitals.

  3. The GP agrees to take responsibility for prescribing Ceredase and the Family Health Services Authority for the area pays for it. However this option is not open where a GP is a 'budget holder'.


Could treatment once started, be ended by financial constraints ?

Prof. Cox said he thought once treatment was started and shown to be effective, there should not be great problems with continuation. Dr. Evans said the evidence of its efficacy was now much more accepted than 18 months ago and costs were comparable to some other rare conditions (e.g. drugs after liver transplants).

Should Ceredase be given prophylactically?

Prof. Cox said that Government policy prefers prevention. Jeremy Manual said there was an economic argument for prevention if you add up the costs of other medical treatment which might become necessary. Dr. Evans said: ''I think it would have been very desirable if the four children I have seen had had preventative treatment. In my opinion if you have a disease and a treatment, you should start early.''

Although all known viruses and bacteria are eliminated in the production of Ceredase, what is the danger of contamination from Creutzfeldt-Jakob disease which occurred in human growth hormone treatment ?

Prof. Cox said although this cannot be ruled out, in the case of human growth hormone the 23 cases (out of thousands who received the drug) were genetically predisposed to the Creutzfeldt -Jakob condition.

Source: Gauchers News February 1993
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