1.0 BACKGROUND AND RATIONALE 
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1.1 Background: Gaucher Disease 
Gaucher disease is an autosomal recessive storage disorder characterized by the 
accumulation of glucocerebroside. Dr. Philippe Gaucher originally described a patient 
in 1882 whose spleen and liver were greatly enlarged. It is now understood that these 
organs are enlarged in Gaucher disease secondary to accumulation of glucocerebroside 
in the lysosomes of macrophages (1,2). In 1965, Dr. Roscoe Brady and his co-workers 
demonstrated that the accumulation of glucocerebroside occurred because an enzyme, 
glucocerebrosidase, was deficient in these individuals (3, 4). The storage or 
accumulation of glucocerebroside in the lysosomes of macrophages results in massive 
macrophage engorgement which is responsible for most of the morbidity and mortality 
associated with Gaucher disease. This process is most marked in spleen, liver and bone 
marrow. Spleen involvement often results in a massively enlarged spleen with 
accompanying anemia, thrombocytopenia, and neutropenia. These same three problems 
are exacerbated by the bone marrow involvement in Gaucher disease. Marrow 
involvement can also lead to bone pain, skeletal malformations, and pathologic fractures. 
Liver involvement can lead to massive enlargement and occasionally cirrhosis. 
Other organs besides liver, bone marrow and spleen can be affected in Gaucher disease. 
The enlarged spleen and liver may make breathing more difficult. The lungs themselves 
may be directly involved resulting in decreased gas exchange. The heart can be 
overworked pumping large quantities of blood to enlarged organs. The skin can show 
changes related to glucocerebroside storage. The most important other organ 
involvement is the central nervous system. Gaucher disease is divided into three types 
based on the extent of nervous system involvement. The most common type of Gaucher 
disease (Type I) does not have neural involvement and therefore is sometimes referred 
to as non-neuronopathic Gaucher disease. Type 2 Gaucher disease has severe 
neurological symptoms and patients usually do not live past the age of two. Type 2 
(infantile Gaucher disease) fortunately is very rare. Type 3 Gaucher disease has slowly 
progressive neurological symptoms and these patients may live to the age of forty years. 
Although more common than Type 2, Type 3 is rare with a cluster in Sweden. 
1.2 Background: Treatment for Gaucher Disease 
Treatment of Gaucher Disease With Bone Marrow Transplantation 
For many years there was only supportive treatment available for people with Gaucher 
disease. Research has emphasized developing treatment focussed on the macrophages 
and their storage of glucocerebroside. Since the cell that is responsible for the pathology 
seen with the disease is the macrophage, attempts have been made to replace the 
defective macrophages. Since macrophages are bone marrow-derived, bone marrow 
transplantation has been used to replace the defective macrophages with new marrow- 
derived macrophages containing functional glucocerebrosidase enzyme. The results on 
patients receiving and surviving the marrow transplant procedure are encouraging. The 
symptoms secondary to spleen and bone marrow involvement have been alleviated (5-9). 
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Recombinant DNA Research, Volume 17 
