Gene therapy salves sensitive nerves
Deactivated herpes virus delivers pain relief.
Neuropathic pain is a devastating nerve disorder for which medicine has no good cure. But a group of scientists at the University of Michigan in Ann Arbor have shown the pain can be eased by a gene transfer technique, in rats at least.
University of Michigan
One of the many factors known to be involved in the generation of neuropathic pain is a reduction of the neurotransmitter GABA in the spinal cord, because GABA has a damping effect on nerve transmission.
Scientists know that an enzyme called glutamic acid decarboxylase (GAD) can increase production of GABA. So the Michigan researchers wondered whether they could boost GABA and relieve pain by adding a gene that encodes for GAD into the spinal cord.
Strike a cord
As a test model, the team damaged the sciatic nerves of a group of rats, which caused them to flinch at gentle heat and touch stimuli. They then used a virus to put the GAD-encoding gene into the spinal cords of the rats. The virus, which was a modified version of the herpes virus that had been engineered to be harmless, also contained a promoter to switch on the gene.
After injection under the skin, the virus did what it does best: it entered peripheral nerves and travelled up them to the nerve centres.
A normal herpes virus would then replicate and travel back down the nerve to the skin where it first entered, causing sores. But the crippled version used by the scientists stayed put in nerve centres and expressed the GAD gene, raising local levels of GABA.
"We just exploited the natural behaviour of the virus," says neurologist David Fink, a co-director of the study, which is published in the Annals of Neurology1.
The treated rats became significantly less sensitive to touch and warmth, whereas rats that underwent a sham treatment did not. The effect lasted up to six weeks: the lifespan of the particular gene promoter that the scientists used.
Fink hopes to start clinical trials of the therapy in humans next year.
- Hao S., Mata M., Wolfe D., Glorioso J. & Fink D. Ann. Neurol., 57. 914 - 918 (2005).