Future Developments for Gauchers Disease including Enzyme Replacement Therapy

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Prof Timothy Cox who heads the Gauchers Centre at Addenbrooke's Hospital, Cambridge, spoke about the history and future developments of Gauchers disease including the use of enzyme replacement therapy.

Prof Cox spoke about the wide range of manifestations in Gauchers disease which has been discovered since the disease was first described in 1882.

'Since then intensive studies have been made worldwide and in 1977 scientists at Cambridge discovered that the cause of the disease lay in the macrophages, the Gauchers cells, where glucocerebrosidase (the fatty substance) is stored.

'From 1983 until now the gene has been mapped, cloned and over 200 mutations have been discovered.

'It is now known that the disease can be found in a wide range of people, from an early still-born child until someone in their 80's who might only have a slight blood defect. It is gratifying that women with Gauchers disease almost invariably have healthy children.'

Enzyme Replacement Therapy

Prof Cox explained that the develop-ment of Ceredase and then Cerezyme has transformed the future for patients with Gauchers disease. He described one of his first patients who had been blood transfusion dependent. A bone marrow donor had been sought but a suitable one could not be found. Fortunately Ceredase had been undergoing trials and he had been able to obtain the drug for his patient from the Genzyme company. The response was dramatic and the patient is well today, ten years later and fully independent and mobile.

'The success of enzyme replacement therapy for Gauchers disease has led the way to develop enzyme replace-ment treatments for other diseases such as Fabry's, Hunter Scheie (MPS1), Hunter's (MPSII), Maroteaux-Lamy (MPSVI) and Pompe's disease.

Gauchers Centres

'In 1998 the Department of Health designated funding for four Specialist Centres to carry out the assessment and management of Gauchers disease and by May 2000 171 patients had attended one of the four Centres. At that time 258 patients were known to have Gauchers disease in the UK: 216 adults and 42 children.

'The Gauchers Centre at Addenbrooke's Hospital has seen 113 referrals of whom four were found not to have Gauchers disease.

Encouragement to Attend

'Some patients don't attend any of the Centres although the Dept of Health wishes to encourage them to do so. It had been suggested that the reasons for their not doing so might be:

'To develop the services of the Centres to patients further, there needs to be earlier and greater access by whatever pathway can be used. An anonymised register comparing the manifestations and other factors that contribute to the effects of the condition should be developed and there must also be improved audits of outcome and applied clinical research. Education at all levels, and at the highest international level, must be encouraged.

'To achieve this, there is a continuing need for a strong partnership between the Gauchers Association and the Centres.


Prof Cox said that the prevalence of Gauchers disease in the general population is estimated to be 1 in 200,000 while in the Ashkenazi Jewish community, it is 1 in 855. It is therefore estimated that there are 35,000 to 40,000 people worldwide who have Gauchers disease. However only 3,000 patients are receiving enzyme replacement therapy and this means less than 10% of sufferers are benefiting from treatment.

'There must be a greater access to therapy and this means the availability of a cheaper drug.'

Protection Against Infection

Prof Cox stressed the importance of protecting patients, who had had their spleens removed, from infection. Infection can be life-threatening and a survey of his patients has revealed a striking number of severe episodes requiring intensive antibiotic treatment.

He advised:

He also said that patients without a spleen should join the MedicAlert Foundation which supplies bracelets and other jewellery with medical details printed on them and keeps a database of relevant information on computer (see below for details).

Possible Treatments

Enzyme replacement therapy is an effective treatment but there is a need to understand its action and possibly potentate (intensify) its effects.

Substrate balance therapy: OGT 918 is still under trial (see page 11 for more details). If treatment is stopped, there is a regression of symptoms but any side effects of the drug also improve when treatment is stopped.

3-4th Generation Bisphosphonate Group of Drugs eg Alendronate, Risedronate or the powerful, injected agent in this class, Pamidronate. These drugs may help remineralise bones in certain groups of people.

Stem Cell Therapy This development remains in the future.

Bone Marrow Transplantation This should only be carried out in exceptional circumstances.

Anti-thrombotic therapy These are anti-clotting agents and may be investigated to see if they can help treat Gauchers patients.

Anti-inflammatory agents: The work of Dr Mary-Teresa Moran at the University of Cambridge, which the Gauchers Association supported, discovered a link between abnormal macrophages in patients with Gauchers disease and inflammation of the surrounding tissues. One agent released by the macrophages implicated in inflammation and bone destruction is Cathepsin K. This product remains the target of at least one major pharmaceutical company. My colleague Dr Paul Schofield who has special insight into this area attests to the early development of anti-cathepsin drugs for use in bone diseases. Clearly patients with Gauchers disease might benefit from the outcome of this research .

Gene therapy Although this therapy has been explored for several years, no affective gene therapy has been developed yet.


Prof Cox said that despite much progress in the last 10 years, especially with Genzyme's development of enzyme therapy, much more needs to be done nationally and internationally to help patients suffering from Gauchers disease and other lysosomal conditions: This included:

Professor Cox concluded by congratulating the Association and its alliance with groups throughout the world on their enormous contributions to the welfare of those affected. He felt the way ahead was rich in opportunity for the thriving patient community.

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Source: Gauchers News March 2002.
© Copyright Gauchers Association 2002