Experimental Adrenoleukodystrophy Treatment

Adrenoleukodystrophy (ALD) is predominantly an X-linked disease that causes brain damage, failure of the adrenal glands and eventually death. It is a rare inherited genetic disorder with child-onset and adult-onset forms. Child-onset is the most severe form and characteristic symptoms include poor memory, aggression, difficulty swallowing, and seizures. Adult-onset, which also includes deterioration in brain function progresses at a slower rate.

Although some girls can suffer the effects of the disease, boys are the most severely affected. This is because they only inherit one copy of the X chromosome and do not have the protective effect of an extra X chromosome.

In 2006 two boys with sex-linked ALD were given gene therapy to try and cure the disorder. Prior to this, treatments included "Lorenzo's Oil" which is a mixture of oleic acid and euric acid that is most effective when applied before the onset of symptoms, and bone marrow transplants. However, the transplants carry a number of risks such as rejection by the body.

The faulty gene is found on the X chromosome and it stops an enzyme from degrading very long chain fatty acids. These accumulate which strips protective myelin from the nerve cells of the brain. A team of researchers led by Patrick Aubourg, a professor at the Saint Vincent de Paul Hospital in Paris believed they could correct the faulty gene by gene therapy.

The scientists took blood stem cells from two 7-year-old boys and infected those cells with a harmless version of the HIV virus that carried corrective copies of the faulty gene into the bone marrow. HIV was used because it can get into the nucleus of non-dividing cells.

This treated bone marrow was then injected back into the two patients.

Scientists observed that the enzyme activity had improved after six months. At sixteen months the stripping away of myelin had stopped, the condition of boys stabilized and they have not got any worse since. According to the researchers they now lead normal family lives.

In fact, the gene therapy trial was so successful that a third patient was also treated, and in November 2009 the scientists announced that they were looking for adult volunteers for a new ALD gene therapy trial.