A World of Difference


Gauchers News Contents


The Dutch Gaucher Association (Gaucher Vereniging Nederland) held its 20th anniversary Symposium on 24-25 October 2003 at Lage Vuursche in Holland. 120 delegates comprising patients, families, doctors, scientists, politicians and pharmaceutical companies heard speakers from Holland, the UK and Germany discuss the progress that has been made for many patients and the need to help those less fortunate than themselves. A report by Susan Lewis.


Henri Termeer, Chairman and Chief Executive Officer of Genzyme Corporation, opened the Dutch 20th anniversary symposium on 24 October, saying: 'It has been a magnificent 20 years. Now nearly 4,000 patients are receiving enzyme replacement therapy around the world.'

He also praised the Dutch patient support group which began in 1983, eight years before enzyme replacement therapy became available. Mr Termeer said that Genzyme was investing millions of dollars every year in research and developing drugs for other rare lysosomal diseases.

When asked about the continuing high cost of Cerezyme, he replied that in future generic drugs may influence the financial aspects of therapy. In addition, patients in China, Egypt and some in Central and Eastern Europe are receiving free treatment through humanitarian aid programmes.

The Difference

'There is a world of difference since before enzyme replacement therapy became available and now,' explained Ria Guijt and Wout Timmerman of the Dutch Gaucher Association (Gaucher Vereniging Nederland).

'People with Gaucher disease have changed from sufferers to people with a treatable disorder. There are even two treatments. 'In the old days, there was not much information, nowadays there is sometimes too much. Papers not only have to be translated from English but also have to be turned into understandable language. 'But there is not only euphoria. Since Gaucher disease gets so much interest world-wide, it appears that increasingly new symptoms are found. It is not always pleasant to know a lot. And then there is sadness since not all patients improve.'

Ten Years of Treatment 'Type 1 Gaucher disease is the most frequently encountered lysosomal storage disorder,' explained Dr Carla Hollak who leads the Gaucher Clinic at the Academic Medical Center at the University of Amsterdam. 'There are 63 patients in Holland and 50 are receiving enzyme therapy. However the clinical picture in Type 1 Gaucher disease is highly variable.

Before the era of enzyme therapy, the treatment was mainly symptomatic: removal of the spleen was performed in patients with severely low blood counts or physical discomfort and orthopaedic procedures were performed in cases of avascular necrosis (where the bone crumbles and dies) or spontaneous fractures. For the painful bone crises, analgesics (pain relief), usually intravenous morphine, were the only choice.

'Nowadays the treatment of Gaucher disease has tremendously improved with the availability of enzyme therapy. Reversal of disease manifestations such as enlarged spleen and liver, low haemoglobin and platelet counts, and bone disease can be achieved, although individual variations in response occur.

'In 1991 my colleagues and I designed a study for adults with Type 1 Gaucher disease that aimed to individualise doses and according to defined criteria adjusted to higher or lower doses. This allowed the determination of the lowest effective dose.

'After over a decade of experience, several conclusions can be made:

  1. The majority of adult Gaucher disease Type 1 patients benefit from relatively low doses of enzyme.
  2. The median (average) dose that showed efficacy during long term follow-up is 15 units per kilogram given every two weeks.
  3. A sub-set of patients only needed 7½ units per kilogram fortnightly whilst another subs-set needed higher doses.
  4. Patients with more severe disease (including active bone disease) need higher doses of between 30-60 units per kilogram every two weeks.
  5. Bone marrow responses occur quickly, also when using relatively low doses of enzyme, measured by bone marrow fat fractions (QCSI).
  6. Chitotriosidase measurement taken from a blood sample is of great value for early and sensitive monitoring of disease and adjustment of doses. 6. Quality of life improves and home treatment is feasible.

'Further studies are currently underway that aim to compare long term efficacy with results from a cohort of patients treated with higher doses of enzyme.

'Following the great success of enzyme therapy for Type 1 Gaucher disease, there are still many issues unresolved. Among them are the long term treatment goals for patients with Type 1 Gaucher disease and how to achieve a more convenient therapy that maintains stable disease in those that have only minimal disease manifestations after several years of enzyme therapy.

'More convenient enzyme therapy schedules as well as switching to oral substrate inhibitors (Zavesca) should be studied in a systematic way.

'Also, the efficacy of enzyme therapy for the treatment of neuronopathic disease, especially Type 3 disease, needs further study. There is a need to find a drug which crosses the blood/brain barrier. 'Combinations of enzyme therapy with substrate reduction are of interest in this respect.

What we have learned from enzyme therapy for Gaucher disease is also of great help for the further development and implementation of already developed enzyme supplementation for other lysosomal storage disorders.

Quality of Life Mineke Ek from the Dept of Haematology at the Academic Medical Center in Amsterdam gave the results of a study into the improvement of the quality of life in patients with Gaucher disease on long term enzyme therapy in the Netherlands.

Enzyme therapy has been available to patients with Gaucher disease in the Netherlands since 1991 but little is known about its impact on the chronic complaints that may affect the patients quality of life. The definition of quality of life is the influence and limitations a disease can have on daily life.

'At the start of enzyme therapy we found that a substantial number of patients suffered from fatigue, chronic pain and restrictions in daily life.

'After one year of treatment, only slight improvement in fatigue and chronic pain was apparent but after eight years of enzyme therapy, improvement was found both with fatigue and pain.

Is there a difference between treatment in Holland and Germany

'About 250 patients have been diagnosed with Type 1 Gaucher disease in Germany with more than 160 patients receiving enzyme therapy,' said Prof Stephan vom Dahl who runs one of the German Gaucher Centres at Heinrich-Heine-Universitat in Dusseldorf.

'Dosage ranges from 20-60 units per kilogram of body weight infused every two weeks but it is important to find the lowest effective dose. 'Only two out of more than 80 Dusseldorf patients discontinued therapy due to weight gain or other personal reasons.

One patient stopped Cerezyme after two years of treatment. After another four years, his red blood and platelet counts dropped and he developed a bone fracture.

'Gaucher cells can be found in every part of the body including the eye. One of my patients was blind in his right eye and could only see movements. After eight months of therapy, he could read again with the help of glasses.

'Basically the features of treatment are similar in Holland and Germany. Also the genetic background in both populations is also similar.

'In Germany, Gaucher patients can be referred to four different centres. The centre at Mainz specialises in children, the one in Rostock sees neurological cases. Prof Claus Niderau, one of the first doctors to apply enzyme therapy in Germany, is at a community hospital in Oberhausen.

'The Dusseldorf Gaucher centre where I work overviews about 90 patients aged from 5 to 82 years old from all over Germany. One third of the patients have no spleen. Patients are usually examined once a year on an outpatient basis. At their first visit patients are examined and blood is taken to include genotyping and chitotriosidase analysis in Prof Hans Aerts laboratory at the Amsterdam Medical Centre.

'Patients get an MRI scan of the legs, an abdominal ultrasound, an electrocardiogram and a thorough neuropsychological testing This comprises computer testing on general reactions, manual coordination and memory. Finally patients can do a test drive on a SMART driving simulator. Every other year, heart ultrasound and pulmonary MR is done to investigate signs of pulmonary hypertension. If necessary patients are evaluated for some days on an inpatient basis and may consult with other experts, eg ophthalmologist, orthopedic surgeon, dentist, neurologist.

'After evaluation of all tests, a medical recommendation is communicated to the patients physician. If treatment has been started, patients are seen after three months and then after another six months. Every year, about three new patients are seen in each center.

'In contrast to the Netherlands where most patients infuse themselves at home, almost all German patients attend local practices for the infusions with some going to local hospitals. Less than 10% use home infusions. Most patients who visit the Dusseldorf centre have the moderate form of the disease and most respond well to treatment. Many could stop taking pain killers after a couple of years.

Some are significantly disabled but almost all of them are capable of leading a normal daily life with no or only little pain, children get a normal education and adults can work in their respective jobs. 'Many patients do some kind of sports and this should be encouraged. One patient had her bone marrow full of Gaucher cells before starting enzyme infusions. However she was a marathon runner and I believe this prevented her bones from deteriorating to a disabling stage before enzyme therapy began.

'Nine out of 44 patients tested have pulmonary hypertension. Three have improved after enzyme therapy and two have maintained stable disease. There is no evidence that pulmonary hypertension gets worse during therapy in the Dusseldorf Gaucher population.

'We have carried out neuro-psychological tests on reaction times, co-ordination and concentration. Preliminary evaluation showed that there was no evidence of any objective reduction in the patients ability.

'In Germany, patients are encouraged but not obliged to attend Gaucher centres. If a physician prescribes enzyme therapy to the patient, the insurance companies usually have to pay. However now, political efforts are being made for therapy in orphan diseases to be directed by experts in their respective fields. Patients are supported by a very active patient organisation led by Ursula Rudat from Lippstadt.


Gauchers News Contents

Source: Gauchers News March 2004.
© Copyright Gauchers Association 2004.