Gene therapy has been used to treat two young boys with a devastating and fatal brain disease called adrenoleukodystrophy (ALD). Two years after treatment, both boys showed signs that the disease had stopped progressing and that there were no serious side effects from the gene therapy. These results, published in the journal Science, show huge promise, both for the future treatment of ALD and for the revival of investigations into the use of gene therapy to treat a wide variety of inherited conditions.
The two boys both suffered from the most common form of ALD, called X-linked ALD, which is caused by a mutation in a gene called ABCD1 and affects around one boy in 20,000. ALD causes progressive damage to the myelin sheath - a fatty coating that protects and insulates nerve cells. Without this coating, nerve cells become damaged and this results in mental and physical disability, loss of sight and hearing, and eventually death within a few years of diagnosis.
The research team at INSERM (The National Institute of Health and Medical Research), Paris, France, took bone marrow samples from the boys and isolated blood stem cells from these samples. They then used an HIV virus (that had first been genetically modified to remove all the genes that make the virus dangerous) as a vehicle to transport a working version of the ABCD1 gene into the stem cells. The stem cells, containing functional ABCD1 genes, were then transplanted back into the boys. After a year, the boys had stopped developing lesions in their brains and two years on their brain function remained stabilised.
The results were equivalent to that seen in boys who receive a bone marrow transplant from a matching donor - the only treatment currently available for ALD. However, donor bone marrow transplants carry significant risks and it is often not possible to find a suitable donor - as was the case with the two boys.
In the past there has been concern about the safety of gene therapy. In one case, boys who received gene therapy for an inherited immune deficiency disorder later developed leukaemia. This was caused by the virus-based vehicle that was used to deliver the replacement gene to cells activating cancer-causing genes in the cells' genome. In the new study, the researchers made modifications to the HIV (human immunodeficiency virus)-based vehicle that they hope will prevent this from happening. Professor Patrick Aubourg, one of the leading researchers on the study, said: 'We have to be cautious. We can't yet say it's safe. But I hope one day this will be a cure.'
The successful use of an HIV-based vehicle is also promising for the future of gene therapy, as it is many times more efficient at delivering corrected genes to cells than vehicles based on other viruses that have been used previously. Professor Auborg said: 'this is the first time we were able to successfully use an HIV-derived vector [vehicle] for gene therapy in humans, and also the first time that a very severe brain disease has been treated with efficacy by gene therapy.'