Therapeutic delivery of a gene to dysfunctional nerves

Medical conditions that affect sensory nerves outside the brain and spinal cord are known as sensory neuronopathies. These conditions, which are extremely painful, include shingles and can be caused by anticancer drugs such as cisplatin. In many sensory neuronopathies, the nerves that are dysfunctional are those in a region of the body known as the dorsal root ganglion (DRG), and these conditions are particularly difficult to treat. However, Lawrence Chan and colleagues, at Baylor College of Medicine, Houston, have developed an approach to target therapeutic genes to nerves in the DRG, and used it to reduce sensory nerve dysfunction in a mouse model of Sandhoff disease, an inherited condition in which many nerves, including those in the DRG, are affected. The authors developed a system to generate helper-dependent adenoviruses that targeted only DRG nerves. These were used to deliver genes to DRG nerves in mice and found to be dramatically more efficient at gene delivery than nontargeted helper-dependent adenoviruses. In mice lacking the Hexb gene, which are consider a mouse model of Sandhoff disease, administration of DRG-targeted helper-dependent adenoviruses carrying the Hexb gene restored Hexb expression in DRG nerves and eliminated sensory nerve dysfunction. The authors hope this approach could be developed for treating different forms of DRG sensory neuronopathies.

Source: Journal of Clinical Investigation