Beverly Davidson, a neurologist at the University of Iowa, US, has been seeking a therapy for children who suffer from lysosomal storage disease, caused by the absence of a particular brain enzyme . 'We know we can't simply deliver the enzyme into the blood and have it access the brain, so we try to devise methods to overcome this problem,' she explains. Her group took barrier endothelial cells and engineered them to produce the missing enzyme and secrete it into the brain itself.3 'Essentially we're turning the BBB into our friend as opposed to our enemy.'
The recombinant DNA that produces the enzyme was delivered into the endothelial cells using a viral vector that the researchers had modified to home in on the diseased brain endothelia. Davidson hopes that the new genetic material will remain in the endothelia for many years. 'We have no evidence that these cells are dividing at all, at least in rodents,' she explains, so a single round of gene therapy could last for decades. The treatment reconstituted enzyme activity throughout the brain of a mouse model; the next step is to move to a large animal model of the disease.