Gene Therapy: Update


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Dr John Barranger began his talk at the US Gaucher Conference in Arlington Virginia on 1-3 October 1999 by saying that the work carried out on Gaucher's disease, and the discovery and effective use of enzyme replacement therapy, has led the way for trials of enzyme therapy for several other diseases and is now leading the way in gene transfer. He described two methods by which he was attempting to do this:


The aim of gene transfer is to put the gene into the tissue macrophages (cells in the liver, spleen and bone marrow) which will then make the enzyme that will make the macrophages work normally,' explained Dr Barranger who is Professor of Human Genetics, Molecular Genetics and Biochemistry at the University of Pittsburgh. He is also the Director of the Human Gene Therapy Applications Laboratory and Co-Director of the Human Gene Therapy Center.

Two Methods of Gene Transfer

We don't have to correct every macrophage, possibly only 25%, and my colleagues and I are currently working on two ways to do this:

We use a retroviral vector to carry the gene to its target. Retroviral vectors have been used in 2,000 people undergoing gene transfer with no untoward effects.

First Trial

In 1994 we carried out our first gene transfer trials on humans using the first method (for a full explanation see Gauchers News July 1998). There were four candidates who were to receive four separate transfers. Three completed the trial. We studied the enzyme and gene activity in all of the patients' white cell lineages, for example in the monocytes, blood cells that come from bone marrow which eventually become macrophages.

'In three of our patients, the activity was short lived. The gene went into the cells but the cells did not engraft (take up the gene).

However in one patient the gene remained for more than three years but eight months after cessation of enzyme replacement therapy, the enzyme in this patient's white cells declined and the presence of the gene could no longer be identified. Despite this, the patient remains well and is not receiving enzyme replacement therapy.

Prof Barranger ended his talk by saying that he hoped to carry out further studies on patients in the year 2000.

Dr Barranger's work is funded by the National Institutes of Health, the National Gaucher Foundation and by Genzyme Corporation.


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Source: Gaucher's News February 2000. © Copyright Gauchers Association 2000