Gene Therapy for Gauchers Disease

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Introducing Professor John Barranger of the University of Pittsburgh, Pennsylvania, USA, Jeremy Manuel said at the Gauchers Association's Second Conference: 'A cure may now be in sight. John Barranger has spent most of his career in research into lysosomal diseases and was instrumental in developing enzyme replacement therapy. He gave the first infusion to the first patient with what we now know as Ceredase.' The picture below shows Professor Barranger explaining one of the main aspects of gene therapy for Gauchers disease.

Professor Barranger explained that Gauchers disease is one of 17 similar medical conditions caused by an enzyme deficiency which can potentially be cured by gene therapy. Bone marrow transplants have been successful in some of these disorders, including Gauchers, and now Gauchers disease is the prototype for developments in gene therapy treatment for the whole group of disorders.

He explained that enzyme replacement therapy (Ceredase) indicates that the gene product can work. 'Partial correction of the enzyme deficiency through gene therapy may be therapeutic.' he said. The feasibility of the treatment has been tested on mice and the conclusion is that the gene transplant lasts the life of the mouse. Test tube experiments with human cells in the laboratory are also successful.

Planned Clinical Trials
Planned clinical trials will involve patients receiving a drug (G-CSF) to stimulate the number of CD34 cells (bone marrow cells) circulating in their blood. After 10 days white blood cells will be collected from the patient by leukophoresis (a machine takes out these cells and returns the rest of the blood to the body). The collected white cells will be put through various laboratory processes to produce a solution rich in CD34 cells and particularly stem cells. Then a genetically corrected retroviral vector will be added. The cells will be checked for contaminants and also that the gene is working to express the enzyme.

This laboratory work will take about a month after which the genetically corrected cells are transplanted back into the patient. If enzymatic activity is not sufficient after three months, this will be repeated up to four times a year. The hope is that sufficient bone marrow cells will become engrafted for the enzyme deficiency to be corrected.

The first clinical trial will start shortly. It is hoped that with only 1% engraftment of the genetically altered bone marrow cells, this could lead to a significant improvement in enzyme available in the body. (It is estimated that Type 1 Gauchers patients only have a 5% to 15% deficiency of enzyme).

Patients in the trial will be monitored every month with blood tests and have a bone marrow biopsy after a year to examine to what extent the genetically altered cells have become establishedin the body and result in clinical improvement.

Commenting on safety, he said that no side effects were shown in mice. In the first trial there will be no destruction of the remaining bone marrow. The retroviral vector cannot reproduce itself. 'None of the 150 human patients worldwide who have received experimental gene transplants have suffered mutagenic (cancerous) effects', he said.

It is possible that a future trial of this gene therapy may be carried out in the UK.

Prof Barranger was asked whether gene therapy for Gauchers disease would be subject to patenting. He replied that the gene was cloned in 1983 and that it was not subject to a patent. However the vector, which transfers the gene to the body, could be patented.

Source: Gauchers News February 1995
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