Gene Therapy for Gaucher's & Fabry Disease Using Viruses & Blood-Forming

Status Completed

Clinical Trial Summary

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 cells.

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.

Clinical Trial Description

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. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT00001234
Study type	Interventional
Source	National Institutes of Health Clinical Center (CC)
Contact
Status	Completed
Phase	Phase 1
Start date	January 1988
Completion date	April 2002

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See also
Status	Clinical Trial	Phase
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Completed	`NCT00004488` - Phase II Randomized Study of Alendronate Sodium for Osteopenia in Patients With Gaucher's Disease	Phase 2
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Completed	`NCT00004294` - Phase I Study of Retrovirally Mediated Transfer of the Human Glucocerebrosidase Gene Into Peripheral Blood Stem Cells for Autologous Transplantation in Patients With Type I Gaucher Disease	Phase 1
Completed	`NCT04656600` - Study to Evaluate Efficacy and Safety of Imiglucerase Treatment in Chinese Patients With Gaucher Disease Type Ⅲ	Phase 4
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Completed	`NCT00176904` - Stem Cell Transplant for Inborn Errors of Metabolism	Phase 2/Phase 3
Completed	`NCT06188325` - A Study to Evaluate Pharmacokinetic Parameters of Eliglustat in Healthy Volunteers Who Are CYP2D6 Extensive or Poor Metabolizers	Phase 1
Completed	`NCT00001416` - Bone Response to Enzyme Replacement in Gaucher's Disease	Phase 2
Completed	`NCT06193304` - A Study to Evaluate Pharmacokinetic Parameters and Safety of Eliglustat Absorption Through the Mouth	Phase 1
Active, not recruiting	`NCT00005900` - Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation	N/A
Completed	`NCT01586455` - Human Placental-Derived Stem Cell Transplantation	Phase 1

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Gene Therapy for Gaucher's and Fabry Disease Using Viruses and Blood-Forming Cells

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms