Who can enter
- Boys with cerebral adrenoleukodystrophy (CALD)
- Age: ≤17 years
Goal
The goal of this study is to determine if an experimental treatment called gene transfer or gene therapy can prevent worsening of CALD symptoms. We also want to determine if this gene therapy can be safely given after treatment with busulfan and fludarabine. These drugs are given as preparation (conditioning) for stem cell transplantation.
"Experimental" means that this study treatment has not been approved as standard by the authorities or any other regulatory body. That will not happen until it is proven to work. However, the designated ethical board has granted approval for the study to be conducted in this way.
Background
Our genes, which we inherit from our parents, are pieces of information that provide the blueprint for the many proteins that keep our cells and our bodies alive. CALD is caused by malfunction of a gene called ABCD1.
The ABCD1 gene, located on the X chromosome, is responsible for making a protein called ALDP. Boys with CALD do not have this protein in their bodies at all or have a protein that does not work properly. This leads to the buildup of very long chain fatty acids (VLCFAs), especially in the brain. These fatty acids cause severe damage to brain cells.
To prevent worsening of CALD, boys who have the disease can receive so-called stem cells from a donor who is not a carrier of the malfunctioning ABCD1 gene. This is called an allogeneic stem cell transplant. The donated stem cells enable the production of new, healthy cells that eventually replace the diseased cells in the brain. Currently, this is the only effective treatment for CALD. Drawbacks are that the body might reject the donor's stem cells, or a suitable donor cannot be found.
In this study, stem cells will be collected from the child with CALD (apheresis), in order to modify these cells with gene therapy. A correctly functioning ABCD1 gene will be added to the stem cells outside the body by means of the "Lenti-D lentiviral vector." This Lenti-D lentiviral vector contains small particles of the human immunodeficiency virus (HIV). To ensure that this cannot lead to infection with HIV, the parts of the HIV virus required for its growth were removed.
The treated stem cells are then transferred back to the child. This procedure is called "autologous" transplantation because the child's own cells are used. The downside, however, is that additional burdensome procedures (apheresis) are required for this treatment. Also, the child's cells may not "catch on." In that case, the child will receive his non-treated cells back.
In case a suitable donor is available, an allogeneic transplant may be preferred. The treatment team will consult with the parents to decide which of the two transplants is finally chosen.