Gaucher's disease is a lysosomal storage disease resulting from glycocerebroside
GLUCOCEREBROSIDE (1) accumulation in macrophages due to a genetic deficiency of the enzyme
glucocerebrosidase. It may occur in patients of all ages. The most severe form, Type 2
Gaucher's Disease occurs in infants who die in the first years of life (with rapidly
progressive neurologic deterioration). The condition is passed from generation to generation
through autosomal recessive inheritance.
Fabry's disease isa genetic disorder (X-linked recessive) due to the absence of the enzyme
a-galactosidase A. The disease is characterized by abnormal collections of glycolipids in
cells (histiocytes) within blood vessel walls, tumors on the thighs, buttocks, and
genitalia(2) decreased sweating, tingling sensations in the extremities, and cataracts.
Patients with Fabry's disease die from complications of the kidney, heart, or brain.
Both conditions are caused by the absence of specific enzymes (3). Patients with these
conditions are missing (3) or have defective genes needed for the normal production of these
enzymes. Studies on the blood-forming cells in bone marrow have lead to gene therapies
using retroviruses as vehicles to carry and insert working genes into abnormal or diseased
This study is designed to measure the safety and effectiveness of transferring working
copies of genes responsible for making missing enzymes into the cells of patients with
Gaucher's or Fabry disease.
This protocol was developed in order to obtain bone marrow stem cells for ex vivo
transduction with retroviruses containing the human glucocerebrosidase gene. We continue to
enter a small number of patients to this protocol each year. Studies with the bone marrow
hematopoietic progenitor cells have enabled us to identify the most effective retroviral
construct currently available in order to carry out gene therapy trials in patients with
Gaucher's disease. The data revealed that a comparatively simple retroviral construct
containing human glucocerebrosidase cDNA driven by the MoLV promoter is highly effective.
We have obtained approval and initiated a Phase I safety and gene marking investigation in
patients with Type I Gaucher's Disease.
Normal and patient volunteers.
Individuals with platelet counts less than 40,000/ul, PT greater than 15 seconds, or PTT
greater than 40 seconds will not undergo bone marrow aspiration.
Individuals with hematologic disorders other than Gaucher Disease, Fabry Disease, or mild
iron deficiency will not undergo bone marrow aspiration.
HIV positive individuals will be excluded from participating.