( for an enzyme called lysosomal alpha-m...)Genetic therapy reverses nervous system damage in animal model of inherited human disease

"Shortly after birth, brain tissue is still physically maturing, which means that there is a particularly important window of opportunity for gene therapy in infants," Wolfe said. "In our study, we could see that gene therapy used during this particular time led to a restoration of damaged neurons, even though the lesions that represent the disease were already extensive."

According to Charles H. Vite, the lead author of the paper and an assistant professor of veterinary neurology at Penn, the treated cats not only demonstrated dramatic clinical improvement, but MRI also revealed that white matter tracks, myelin, in the brain had been largely restored.

"As we move toward the clinical use of this therapy in humans, we must develop and utilize non-invasive methods to monitor the regression of the disease following treatment," Vite said. "The ability to monitor the improvement in brain myelination in alpha-mannosidosis using imaging allows the clinician to see improvement in brain pathology without the need for brain biopsy."

"Lysosomal storage diseases are particularly good candidates for gene therapy because, as we show with LAMAN, active enzymes from genetically corrected cells will be secreted into brain tissue and taken up by neighboring cells, Wolfe said. "In this case we see that storage lesions throughout the brain had been greatly reduced, even though gene transfer was limited to areas surrounding where injections had been made."

The large animal study also demonstrated that only a limited number of injections are necessary to introduce the working LAMAN gene, one of the first steps that will prepare this particular gene therapy for practical use in humans. The gene is transported via a neutralized virus that "infects" cells with the functioning gene. Since the blood-brain barrier would block the virus carrying the gene if it were circulating in the bloodstream,
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Source:University of Pennsylvania