Gene therapy is to live up to its promise to end, a rare fatal brain disease in young boys. In a new study presented in Washington, DC, yesterday, at the annual meeting of the American Society of Gene and Cell Therapy, all but one of 17 boys with adrenoleukodystrophy (ALD) remained relatively healthy for up to 2 years after a virus designed to deliver a gene in their cells to reconstruct a missing protein needed by the brain. The results, which expand on a prior pilot study, ALD bring this therapy one step closer to the clinic.
About a 21 000 boys are born with ALD, which is caused by a defect in a gene on the X chromosome that prevents cells from making a protein that cells need to treat some fat-females have a copy backup gene on their second chromosome X. Without this protein, the fatty acids accumulate and gradually destroys the myelin sheaths that protect the nerves of the brain. In the cerebral form of ALD, which begins in childhood, patients rapidly lose vision and mobility, death usually by age 12, the disease reached a certain degree of fame with the 1992 film Oil Lorenzo , inspired by the struggle of a family to extend the life of their son with a home remedy
the only treatment currently approved for ALD is a bone marrow transplant -. white blood cells in the marrow go to the brain and turn into glial cells that produce normal ALD proteins. But bone marrow transplants carry many risks, including immune rejection and donor matching funds can not always be found. Alternatively, in the late 00s, French researchers treated the bone cells of two boys with a modified virus carrying the ALD gene. They reported in Science in 09 that halted the progression of the disease.
Now, the researchers tested a similar therapy in a large trial sponsored by the biotechnology company Bluebird Bio. The scientists removed the blood cells from 17 boys with cerebral ALD from 4 to 13 years and treated the cells with a modified HIV virus carrying the gene for ALD protein. They then returned the new cells in patients. Within 6 months, 16 patients stabilized, reported David Williams of Harvard Dana-Farber Cancer Institute affiliated with the University and Children's Hospital Boston. In brain scans taken until two years later, most had no other signs of inflammation or loss of myelin. And 16 of the 17 had no signs of neurological decline such as loss of vision or trouble walking.
Williams called the results "very exciting." None of the patients showed signs that the gene was inserted in the wrong place on the genome and triggers the uncontrolled growth of certain cells, a problem that led to leukemia in some patients in a clinical trial of gene therapy previously. (One patient in the study ALD had a bladder infection and other irregular heartbeats that may have been related to the therapy, but both recovered.)
The boys are not completely in good health. Gene therapy does not reverse ALD, and the disease can progress within a few months after the treatment needed for the modified cells into glial cells and make the ALD protein. But they are in school and live a normal life. "The key is to transplant early," shortly after a child is diagnosed with ALD, Williams said.
The results are "very impressive," says gene therapy researcher Cynthia Dunbar of the National Heart, Lung, and Blood Institute in Bethesda, Maryland. It notes that the study is also a great place logistics realization, because ALD is so rare, the trial took seven sites in five countries, where the genetically modified cells of each patient were carefully shipped from a site central manufacturing.
Bluebird needs to wait until all patients 2 years of treatment before applying to the US Food and Drug Administration (FDA) for regulatory approval. Although European authorities have already given the green light to gene therapy for a rare disease and should soon approve a second FDA has not approved a single gene therapy.
0 Komentar