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Gene therapy rescues nerve degeneration in diabetic rats and rabbits
By Bijal P. Trivedi

Researchers have used gene therapy to halt and reverse nerve degeneration in diabetic rats and rabbits.

Introducing blood vessel-promoting genes into diabetic animals has reversed nerve damage caused by poor circulation. The team, led by Jeffrey Isner of Tufts University School of Medicine in Boston, Massachusetts, injected the VEGF-1 and VEGF-2 genes into the leg muscles of diabetic rats and rabbits to stimulate blood vessel growth around degenerating nerves.

Eight weeks after the rabbits had received the VEGF gene the researchers found that the number of blood vessels surrounding a nerve in the leg rose from 16 to 49, which was similar to non-diabetic animals. The results were similar with both forms of VEGF.

The increase in blood vessel number was also accompanied by the restoration of motor and sensory nerve functions. Measurements of electrical activity within the nerves indicated that they were conducting signals in a manner similar to healthy animals.

Comparable results were seen in rats.

Diabetes is a chronic disease caused by the inability to produce insulin—a hormone that regulates blood sugar levels. High sugar levels destroy blood vessels that then become leaky, and reduce blood flow. Poor circulation leads to irreversible nerve damage throughout the body. Deterioration of nerves in the legs, feet and hands can make injuries more likely because individuals are less sensitive to pain. Foot ulcers are particularly common in diabetics, and can be so severe that amputation is required. The rate of leg amputation in diabetics is 15 times higher than in non-diabetics.

While animal models do not mimic all aspects of the human disorder, this study does suggest that the potential of VEGF therapy for treating irreversible nerve degeneration in humans should be explored.

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Schratzberger, P. et al. Reversal of experimental diabetic neuropathy by VEGF gene transfer. J Clin Invest 107 (May 2001).

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