Gaucher disease is a lysosomal storage disease resulting from glucocerebroside accumulation
in macrophages due to a genetic deficiency of the enzyme glucocerebrosidase. It may occur
in patients of all ages. The condition is marked by enlargement of the liver and spleen
(hepatosplenomegaly), low blood and platelet counts, and bone abnormalities. The condition
is passed from generation to generation on via autosomal recessive inheritance. There are
actually three types of Gaucher disease.
Type I is the most common form. It is a chronic non-neuronopathic form, meaning the disease
does not affect the nervous system. The symptoms of type I can appear at any age.
Type 2 Gaucher disease presents prenatally or in infancy and usually results in death for
the patient. Type 2 is an acute neuronopathic form and can affect the brain stem. It is
the most severe form of the disease.
Type 3 Gaucher disease is also neuronopathic, however it is subacute in nature. This
means the course of the illness lies somewhere between long-term (chronic) and short-term
Currently there is not a cure for Gaucher disease. Treatment for the disease has
traditionally been supportive. In some severely affected patients, bone-marrow transplants
have corrected the enzyme deficiency, but it is considered a high-risk procedure and
recovery can be very slow. Enzyme replacement therapy is another therapy option and has
been approved by the Food and Drug Administration (FDA) for use in type 1 patients.
PEG-glucocerbrosidase is a drug designed to clear out the accumulation of lipid
(glucocerebroside) from the blood stream. The drug is actually an enzyme attached to large
molecules called polyethylene glycol (PEG). The large molecules of PEG allow the enzyme to
remain in the blood stream for long periods of time. By modifying glucocerebrosidase with
PEG, it is believed that smaller doses will be required, meaning a reduction in cost for
the patient and more convenient administration of the drug. The purpose of this study is to
evaluate the effects and safety of enzyme replacement therapy using PEG- glucocerebrosidase
for the treatment of Gaucher disease.
The purpose of this clinical study is to evaluate the biochemical and therapeutic effects
and safety of enzyme replacement therapy using polyethyleneglycol (PEG) modified
glucocerebrosidase for the treatment of Gaucher disease and to evaluate the benefit to risk
ratio. The study is designed to determine the safety and efficacy in Gaucher patients of
recombinantly produced human glucocerebrosidase, which is PEG modified. Parameters to be
monitored include hemoglobin, platelet counts, organ size, and extent of bony involvement.
Pharmacokinetic, pharmacodynamic, and antibody studies will also be evaluated.
Patients must be at least 3 years of age.
Must have a biochemically confirmed (enzyme) and/or genetically confirmed diagnosis of
type 1 or type 3 Gaucher disease.
Clinical or laboratory signs suggesting need for therapy which will include at least 2 of
the following: hemoglobin less than 11 gm/dl; platelets less than 90,000/mm(3);
hepatomegaly and/or splenomegaly.
Patient/Guardian must provide written informed consent.
No pregnant or breast feeding women.
No women/men of reproductive potential unless they agree to use an effective contraceptive
No patients treated with alglucerase or imiglucerase during the 6 months prior to study
No patients with the diagnosis of type 2 Gaucher disease.
No patients who have a life-threatening disease or are gravely ill.
No patients who have rapidly progressing fatal illness or concomitant malignancy.
No patients who have a chronic infectious disease including HIV or hepatitis B.
No patients chronically on other medications which may interfere with the drug's
metabolism or activity.
No patients who received blood transfusion within a month prior to study entry.