A new gene therapy has halted the progression of a fatal degenerative brain disease in a small study of affected boys.
Until now, the only effective treatment available for patients with the rare disease cerebral adrenoleukodystropy (ALD) was stem cell transplantation from a compatible donor. Yet the new therapy uses the patient's own stem cells.
'The impact of this trial has been phenomenal,' said Dr Florian Eichler at Massachusetts General Hospital in Boston, who co-led the study. 'Boys without a donor match for stem-cell transplant were often passing away within a year or two of their diagnosis. Now, with early diagnosis and gene therapy, these boys are living longer and some are thriving enough to play sports and participate in other normal day-to-day activities.'
In the global, multi-centre study, researchers collected stem cells from the blood of 17 boys aged four to 14 with the severe cerebral form of ALD, also known as 'Lorenzo's oil' disease after its depiction in a 1992 film of this name.
These patients have a faulty gene on the X chromosome which causes a build-up of fatty acids that damage the protective myelin sheath around nerves, leading to motor problems and loss of the ability to walk and talk within a few years.
The scientists used an inactive form of the HIV virus to insert a correct version of the faulty gene into the stem cells, before injecting them back into the bloodstream of the patient.
Two years after receiving the treatment, 15 of the 17 patients were functioning normally and free of major disability.
'This appears to be a terrific new therapy for many kids who had little hope before,' said Dr David Williams, president of the Dana-Farber/Boston Children's Cancer and Blood Disorders Centre in Massachusetts, and senior study author. He added that the use of a patient's own, gene-modified stem cells minimises the risk of significant side effects.
The work is ongoing with eight more boys being enrolled onto the study, and long-term follow-up of the patients.
The trial opens new avenues for using gene therapy in brain diseases. Dr Theodore Friedmann at the University of California San Diego School of Medicine, who was not involved in the study, told The New York Times: 'Many think the central nervous system is intractable and unapproachable. This study proves them wrong.'
The results of the clinical trial, published in The New England Journal of Medicine, brings this treatment closer to the clinic - with the biotechnology company bluebird bio which sponsored the study in talks with US and European regulators.