Technology & Services Section
Gaucher Disease and the Impact of Cerezyme ®
a report by
Hans Ebels, MD
Genzyme Europe BV
Cascade of Reactions Leading to abdominal pain and diarrhoea/frequent stools, and
Dysfunction of Organs experiencing ‘stitches’ or stinging pain in the side
when playing or exercising. It is likely that the
Gaucher disease patients have deficient activity of the consulted physician will first suspect a common
enzyme glucocerebrosidase. Progressive macrophageal harmless disorder such as a viral infection. Repeat
accumulation of glucocerebroside leads to the massive checking, though, should show repeat abnormalities,
enlargement of macrophages, also known as ‘Gaucher and may raise the index of suspicion of a more serious
cells’, initiating a cascade of reactions early in life. disorder requiring further diagnostic work-up.
Gaucher cells can be found wherever macrophages
normally reside and their presence underlies the major The Spectrum of Clinical
clinical manifestations. These enlarged cells Manifestations
hypersecrete chemokines and (pro-) inflammatory
cytokines attracting alternatively activated macrophages For many years, the main focus in clinical
inducing a low-grade chronic inflammatory management was on the visceral and haematological
response,1,2 eliciting secondary processes, leading to Gaucher manifestations. It is in recent years that the
further pathology. A large mass of these metabolically extent, progression and clinical consequences of
overactive Gaucher cells has significant indirect effects skeletal involvement have become adequately
on weight gain, growth and caloric requirements3 and appreciated. It is now acknowledged that the bone
may be responsible for a skinny appearance with complications and the often irreversible consequences
muscle wasting and low weight-for-height. Gaucher thereof are usually the most debilitating aspect of
disease, if untreated or managed sub-optimally, can Gaucher disease. Bone abnormalities are seen in a
cause damage to cells, tissues and organs throughout variety of presentations, both symptomatic and
the body and may lead to potentially irreversible, asymptomatic, in the majority of patients.5
functional loss or even to early death.
Bone marrow infiltration with Gaucher cells (and
How Gaucher Patients Come to other activated macrophages) seems to be the first step
Medical Attention with secondary processes presumably leading to
abnormalities in mineralisation and bone structure
It is unlikely that individuals with Gaucher disease will (bone remodelling failure). The reduced fat content of
come to medical attention with full-blown classical bone marrow is best visualised using magnetic
textbook Gaucher symptoms. The first medical resonance imaging (MRI) in which the T1-weighted
consultation is likely to occur during childhood when signal is decreased in affected areas. Bone crises,
symptoms such as bone pain, bruises, nose bleeds and believed to be due to oedema and resembling crises in
fatigue are still more subtle and the spleen is mildly sickle cell anaemia, are more prevalent in children
enlarged.4 Further seemingly innocuous symptoms than in adults. Mostly, clinical proof of osteonecrosis is
may include gastrointestinal disturbances, e.g. upper present. Otherwise, various types of bone pain may
1. Boven L A, van Meurs M, Boot R G et al., “Gaucher cells demonstrate a distinct macrophage phenotype and resemble
alternatively activated macrophages”, Am. J. Clin. Pathol. (2004);122(3): pp. 359–369.
2. Deegan P B, Moran M T, McFarlane I et al., “Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher
disease”, Blood Cells Mol. Dis. (2005); 35(2): pp. 259–267.
3. Hollak C, “Abnormal Energy Expenditure and Glucose Metabolism in Type 1 Gaucher Disease”, Gaucher Clin. Persp.
(1999); 7(1): pp. 1–3.
4. Pastores G M, Weinreb N J, Aerts H et al., “Therapeutic goals in the treatment of Gaucher disease”, Semin. Hematol.
(2004); 41(4 Suppl 5): pp. 4–14.
5. Pastores G M, Wallenstein S, Desnick R J, Luckey M M, “Bone density in Type 1 Gaucher disease”, J. Bone & Mineral
Res. (1996); 11(11): pp. 1801–1807. 1
BUSINESS BRIEFING: EUROPEAN PHARMACOTHERAPY 2006
Technology & Services Section
occur in Gaucher disease, including dull, achy, non- initial clinical studies and independent published
specific, or intense and localised pain. Skeletal growth case series: clinically significant responses in systemic
retardation is very common. Children may reach and parameters can be expected to occur in type 1 and
close-off puberty at a later age than normal youngsters. type 3 Gaucher patients treated with the best
standard of care – Cerezyme.4 Cerezyme is
In the past, huge spleens up to 70 times normal size and efficacious in completely or partially reversing or
deformed by infarction, necrosis and fibrosis could be preventing further deterioration of Gaucher disease
encountered, but nowadays, with improved medical manifestations in most disease domains, including
care, splenomegaly is likely to be more subtle. Liver the skeletal compartment. Its safety profile is well-
enlargement – frequently less marked and occurring defined and remarkably positive. Furthermore,
later than splenomegaly – may add to abdominal Cerezyme infusions are generally very well
distension, discomfort and early satiety. Haematol- tolerated; increasingly, such infusions are
ogical abnormalities result from displacement of administered in the patient’s home.
haematopoietic elements and sequestration of blood
products in the enlarged spleen. Chest radiography International panels of physicians with expertise
may detect the bilateral reticulonodular infiltrates. in Gaucher disease have collaborated on
developing therapeutic and outcome monitoring
Impact on Quality of Life recommendations, both for children 7,9,10 and
adult 11,12 patients. In addition, based on the
Gaucher disease can severely impair the quality of life collective efficacy data, a disease management
of patients and their families and significantly reduce model for Gaucher disease was designed. This
life expectancy.6 Whether on their own or in model, encompassing recommendations for initial
combination, symptoms, particularly skeletal assessment and on-going monitoring and for setting
complications, may diminish patients’ feelings of individualised therapeutic goals, enables physicians
well-being and functional health and prevent them caring for Gaucher patients to optimise their
from working or pursuing family or leisure activities. clinical management.4
Especially in the paediatric age group, this chronic
disease can lead to limited attention span, learning Genzyme, committed to the development of
difficulties, low self-esteem, psychosexual problems products and services to satisfy, currently, unmet
and behavioural abnormalities.7 medical needs, will contribute to furthering
knowledge about Gaucher disease, and will gladly
Cerezyme® (Imiglucerase) Enzyme assist researchers and healthcare professionals to
Replacement Therapy achieve this. Building on Genzyme’s experiences
with Cerezyme, enzyme replacement therapies are
To date, thousands of Gaucher disease patients have currently also available for mucopolysaccharidosis I
benefited from Cerezyme.8 The rationale for this (Aldurazyme ®, laronidase) and Fabry disease
therapy is very simple: replace the deficient enzyme. (Fabrazyme ®, agalsidase beta). Should it be
Clinical outcomes, collected over a period of approved by the European Medicines Agency
approximately 15 years from the International (EMEA), Myozyme® – as enzyme replacement
Collaborative Gaucher Group (ICGG) Registry therapy for Pompe disease – will become available
cohort of some 4,000 patients, mirror the results of in the near future. ■
6. Damiano A M, Pastores G M, Ware J E, Jr, “The health-related quality of life of adults with Gaucher’s disease receiving
enzyme replacement therapy: results from a retrospective study”, Quality of Life Res. (1998); 7(5): pp. 373–386.
7. Grabowski G A, Andria G, Baldellou A et al., “Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and
assessment. Consensus statements”, Eur. J. Pediatr. (2004); 163(2): pp. 58–66.
8. Cerezyme (imiglucerase) Summary of Product Characteristics, http://www.emea.eu.int/humandocs/Humans/EPAR/
9. Baldellou A, Andria G, Campbell P E, Charrow J, Cohen I J, Grabowski G A et al., “Paediatric non-neuronopathic
Gaucher disease: recommendations for treatment and monitoring”, Eur. J. Pediatr. (2003); 163: pp. 67–75.
10. Charrow J, Andersson H C, Kaplan P, Kolodny E H, Mistry P, Pastores G et al., “Enzyme replacement therapy and
monitoring for children with type 1 Gaucher disease: Consensus recommendations”, J. Pediatr. (2004); 144(1): pp.
11. Weinreb N J, Aggio M C, Andersson H C, Andria G, Charrow J, Clarke J T et al., “Gaucher disease type 1: Revised
recommendations on evaluations and monitoring for adult patients”, Semin. Hematol. (2004); 41(4 Suppl 5): pp.
12. Andersson H C, Charrow J, Kaplan P, Mistry P, Pastores G M, Prakesh-Cheng A et al., “Individualization of long-
term enzyme replacement therapy for Gaucher disease”, Genet. Med. (2005); 7(2): pp. 105–110.
BUSINESS BRIEFING: EUROPEAN PHARMACOTHERAPY 2006