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Home On the News Gene therapy could cure Lorenzo’s Oil brain disease

Gene therapy could cure Lorenzo’s Oil brain disease

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November 6, 2009

A devastating brain disease that kills boys by the time of adolescence has been stopped in its tracks by a gene therapy that raises hope for thousands of families.

The treatment has halted the development of adrenoleukodystrophy (ALD) — the genetic disorder featured in the film Lorenzo’s Oil — in two Spanish boys aged 7 who would otherwise have suffered progressive and ultimately fatal brain damage. A third boy has also been treated, but too recently for doctors to know whether it has been successful.

The work suggests that ALD can be prevented by correcting the mutant gene responsible. The treatment may also be suitable for adults with a late-onset form of the condition.

Another benefit should be to advance the development of gene therapies for other inherited conditions, such as sickle cell anaemia and thalassaemia, by demonstrating a powerful new approach to altering defective DNA.

“This gives children with ALD and their families the hope of a future,” said Patrick Aubourg, Professor of Paediatrics at Paris Descartes University, who led the research. “We have to be cautious. We can’t yet say it’s safe. But I hope one day this will be a cure.”

Nathalie Cartier, his colleague, said: “The cognitive function of these boys has completely stabilised. They will still have some minor consequences of cerebral ALD but they go to school, have a normal family life and social life. Children who don’t receive treatment are in a terrible state. They don’t feed, don’t talk, they go blind and deaf, and eventually die.”

The disease, which affects one boy in 20,000, is caused by a mutation in the ALD gene. The mutation causes the loss of protective myelin coverings from nerve cells. In about 55 per cent of cases, symptoms start between the ages of 6 and 8, causing brain damage and death by the teenage years. The remaining 45 per cent of male carriers develop a less severe form in adulthood, though this can still cause brain damage, paralysis and death.

ALD can sometimes be alleviated by Lorenzo’s Oil, a drug created in America by Augusto and Michaela Odone to treat their son, Lorenzo, whose story is told in Lorenzo’s Oil starring Nick Nolte and Susan Sarandon. Lorenzo, once the oldest survivor of childhood ALD, died last year at 30.

The disease can also be treated with bone marrow transplants, which supply stem cells to replenish brain and spine tissue. These, however, require a perfectly-matched donor, and carry significant risks. “Mortality is 15 per cent in children and 30 to 40 per cent in adults,” Professor Aubourg said.

In the study, published in the journal Science, researchers turned to gene therapy for two boys for whom no donor was available. They removed bone marrow from each, then infected blood stem cells with a virus engineered to carry a working copy of the ALD gene. The boys’ remaining bone marrow was destroyed, before their modified stem cells were re-infused.

The boys, now aged 9 and 10, continued to develop brain lesions for a year but their condition has since stabilised. They have suffered no further lesions or cognitive decline. Professor Aubourg said: “I think in a relatively short time we could propose gene therapy instead of classical bone marrow transplants for children, perhaps unless there is a perfect match from a brother or sister donor.”

The scientists said they hoped that the treatment would work on a one-off basis, though the patients will have to be followed up for longer periods to confirm this.

The study is the first to show that a virus known as a lentivirus — a disabled form of HIV — can be used to correct genetic defects in human cells. This should assist the development of gene therapies for other diseases.

Mark Liley, the founder of Oliver’s Army , a British ALD charity, said: “This is great work that could make a real difference.”

Mr Liley, from Orston, near Nottingham, founded the charity in memory of his son, Oliver, who died of the disease at 14. Oliver was a show-jumper who had represented England when he began to show symptoms at 12. “He became forgetful, he couldn’t remember his jumps, and his handwriting started to deteriorate,” his father said. “Then his legs went, then one arm, then the other. He became blind and deaf, he couldn’t swallow, and he had to be fed through a tube. It took nearly three years until he passed away, just before his 15th birthday.”

His elder brother, Sam, 20, has also inherited the mutation. He remains free of symptoms but is at risk of the adult-onset form of the disease.“I go for an MRI once a year and a check-up every three months, and if something changes in the scan we’ll go for a bone marrow transplant,” he said.

He is encouraged by the development of the new gene therapy. “It is something I would consider,” he said. “I’m more than happy to try things as long as there’s no risk of me popping it. It’s great that this research is getting somewhere, and that there might be a cure for the disease.”

The Liley family founded the charity Oliver’s Army in memory of their son, which has raised about £450,000 for adrenoleukodystrophy research since his death.

Last Updated on Tuesday, 10 November 2009 11:56  

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