Gene Therapy for X-ALD
February 9th, 2010 |
Science. 2009 Nov 6;326(5954):818-23.
Drs Nathalie Cartier and Patrick Aubourg and colleagues (Saint Vincent de Paul Hospital, Paris, France) have successfully treated two 7-year old boys with early signs of cerebral ALD using gene therapy. These boys were candidate for allogeneic hematopoietic stem cell transplantation (HSCT), but matched donors were not available.
Bone-marrow cells were extracted from the patients. Before therapy, no ALD protein was detectable in the patients’ blood cells. In the laboratory, a normal copy of the X-ALD gene was inserted in the bone marrow cells using a virus derived from HIV. The patients underwent chemotherapy to eradicate their bone marrow to stop it from producing further stem cells. They then received an infusion of their own genetically corrected stem cells carrying the normal gene.
The two patients were followed for 24 and 30 months. Over this period, 15% of their blood cells demonstrated expression of the normal ALD protein. The VLCFA were reduced by 38% in the plasma of the patients.
Brain MRI scans and cognitive tests showed that progression of the cerebral disease stopped after 14-16 months. The patients remained stable since then. The demyelinating lesion observed in the auditory pathway of one patient was reversed. The arrest of progressive cerebral demyelination in these two children represents a clinical outcome that is comparable with the clinical outcome of HSCT.
