Gene Therapy Developed for Children with ALD

There is new hope for children suffering from ALD. French researchers under the lead of Patrick Aubourg from the Saint-Vincent-de-Paul hospital in Paris developed a gene therapy to treat ALD. The results were presented at the ESGCT 2007 conference currently taking place in Rotterdam, Netherlands.

Adrenoleukodystrophy (ALD) is an x-linked metabolic disorder. Patients with the disease miss an enzyme that dissolves saturated very-long-chain fatty acids (VLCFA) in the central nervous system. This causes a progressive neurological deterioration. The brain function deteriorates because the protective myelin sheath, a fatty coating around the nerve cells of the brain that maintains the nerve signals, is slowly stripped away. Therefore, the brain's ability to tell the nerves and muscles what to do deteriorates.

The disease is incurable and primarily affects males, because females have a second X chromosome, which, if healthy, can balance out the negative affects of the abnormal X chromosome. The disease is usually diagnosed between the ages of four to ten. As the disease is progressive it usually leads first to speech and coordination problems, then dementia, which can quickly lead to a vegetative state and ultimately the death of the patient within ten years of the onset of symptoms.

ALD became widely known through the movie "Lorenzo's Oil" (1992) with Nick Nolte and Susan Sarandon, who play the part of the parents of a child with the disease. The movie is based on the real life of the boy Lorenzo Odones, whose parents developed an oil therapy and special diet, which helps with the ALD treatment and appears to slow down the progress of the disease. Lorenzo, now 29, is still alive. Unfortunately, although the oil treatment combined with a special diet has delayed the progression of ALD, Lorenzo is at this point totally paralyzed.

The French team of researchers now developed a gene therapy that might offer a cure for this deadly disease. The team uses a harmless version of the HI-virus as a Trojan horse. With the help of this virus a corrected gene is implanted in the patient's bone marrow. Through this therapy the patient's abnormal genes are supposed to be exchanged for the normal ones thereby stopping the disease.

The researchers observed promising results half a year after the gene therapy was started. In some patients the production of the enzyme responsible to reduce the VLCFA began to increase. Further studies are necessary to see the long-term effects of the treatment.