Scientists halt brain disease with new gene therapy

By Kate Kelland

LONDON (Reuters) - Scientists have managed to halt a rare and fatal brain disease with an experimental gene therapy technique using a deactivated version of the AIDS virus, a study published on Thursday showed.

The international team used a disabled form of human immunodeficiency virus (HIV) to deliver working genes to two boys with the brain disease X-linked adrenoleukodystrophy (ALD). Their success may help shape future treatment.

Patrick Aubourg of Inserm-University Paris Descartes, who led the study, said it was the first time scientists had successfully used an HIV-derived delivery technique for gene therapy in humans, and the first time gene therapy had been used effectively in a severe brain disease.

"Up to now we have treated two boys ... and we can say with confidence that more than two years after gene therapy their brain disease has been arrested," he said.

Featured in the 1992 movie "Lorenzo's Oil," ALD is a rare hereditary condition caused by a deficiency of a protein involved in fatty acid degradation.

Sufferers gradually lose the myelin sheath, a protective layer coating the brain's nerve fibers, leading to disabilities such as blindness, deafness, seizures and progressive dementia.

X-linked ALD, the most common form, affects boys from around 6 years old, and they usually die before reaching adolescence.

The disease can be halted using bone marrow transplants because the donor marrow includes cells that develop into myelin-producing cells. But finding a matching donor can be difficult and take time, and the transplant is risky.

Reporting the results in the journal Science, Aubourg said the two study patients had shown as great an improvement as they would have with bone marrow transplant.

Gene therapy involves inserting a working gene to replace a faulty one.

Its development has suffered a number of setbacks, including the death 10 years ago of an American teenager in one experiment and two cases of leukemia in boys treated for severe combined immunodeficiency (SCID) in 2002.

More recently, though, doctors have made encouraging steps. A study published in October showed success with gene therapy in a type of inherited blindness call Leber congenital amaurosis [ID:nN24142112] and in January a follow-up study of SCID children concluded that eight of 10 treated seemed to be cured.

In their study, Aubourg and his team took blood stem cells from the patients' bone marrow and used the new vector system to genetically alter them by inserting a working copy of the ALD gene. The modified cells were then put back into the patients.

Two years later, the scientists still detected ALD proteins in the patients, and the disease had stopped getting worse.

Aubourg said he expected this gene approach could be used in the future for many more patients needing bone marrow transplants.

(Editing by Elizabeth Fullerton)