Gaucher disease is a lysosomal storage disease resulting from glycocerebroside accumulation
in macrophages due to a genetic deficiency of the enzyme glucocerebrosidase. It may occur in
adults but occurs most severely in infants, in whom cerebroside also accumulates in neurons.
Patients with Gaucher's disease experience enlargement of the liver and spleen and bone
destruction. The condition is passed from generation to generation through autosomal
recessive inheritance. There are actually three types of Gaucher's disease.
Type I is the most common form. It is a chronic non-neuronopathic form, meaning the disease
does not affect nerve cells. The symptoms of type I can appear at any age.
Type II appears in infancy and usually results in death for the patient. Type II is an acute
neuronopathic form and can affect the brain stem. It is the most severe form of the disease.
Type III 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 (acute).
The purpose of this study is to examine the effects of enzyme replacement therapy on
patients with Gaucher's disease, specifically those types directly affecting the nervous
Patients with Gaucher's disease types II and III will be selected to participate in the
study and receive enzyme replacement therapy. Patients participating will undergo a variety
of tests to measure levels of hemoglobin concentration, liver volume, and spleen volume.
Improvements in these measures will be compared other laboratory tests measuring the
involvement of the nervous system.
The purpose of this study is to examine the effects of enzyme replacement therapy in
patients with neuronopathic Gaucher's disease and to investigate the pathogenesis of their
neurological signs and symptoms. Macrophage-targeted glucocerebrosidase will be administered
by intravenous infusion under the supervision of the patient's private physician at an
initial dosage of 60 to 120 IU per kg of body weight weekly or every other week. Patients
will be categorized as treatment responders if they display a clinically significant
increase in hemoglobin concentration and a reduction in hepatic or splenic volume.
Improvement in these parameters over time will be correlated with measurements for metabolic
encephalopathy and radiologic, electrophysiologic and psychometric measurements of
- INCLUSION CRITERIA:
1. All patients with neuropathic Gaucher's disease who have a partial or complete
horizontal supranuclear gaze palsy or a genotype associated with neurological
2. All candidates must be serologically nonreactive for hepatitis B and human
immunodeficiency (AIDS) virus. HIV positive patients will be excluded because of
the effects of the latter illness on cognitive performance.
3. Individuals with neoplastic disease will be excluded.
4. The general health and well being of each candidate must be sufficient to allow
for a modest amount of blood drawing, collection of appropriate urine and spinal
fluid specimens and performance of necessary roentgenographic and magnetic
resonance (MR) imaging studies. In addition, each candidate must be able to
return to the National Institutes of Health (NIH) on a regular basis dictated by
disease severity for monitoring of laboratory parameters.
1. Patient who participates in a clinical study of an investigational therapeutic agent
for Gaucher Disease.
2. Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand
the nature, scope, and possible consequences of the study.
3. Patient is unable to comply with the protocol, e.g., uncooperative with protocol
schedule, refusal to agree to all of the study procedures.