NIH scientists are attacking chronic pain with a novel form of gene therapy that targets the spinal cord. Though still in the animal testing stage, this approach has overcome one of the major obstacles to gene therapy as a way to manipulate spinal cord function. Rather than injecting genes directly into a localized area of the spinal cord, the pain-relieving gene is introduced into the sheath of tissue that surrounds the cord. From that strategic location, the gene can pump out its product and bathe many nerves, thus extending the range of its pain-numbing effect. The investigators hope that this simplified approach can be used to generate a variety of products in the tissue surrounding nerves, including factors that could stimulate new nerve growth.

The study, carried out by scientists from the National Institute of Dental and Craniofacial Research (NIDCR) and the University of Pennsylvania, was reported in the May 1 issue of Human Gene Therapy.

"We are totally pumped up that this approach is working in an animal model," said Dr. Mike Iadarola, chief of NIDCR's Neuronal Gene Expression Unit. "The animal studies have shown us that genes are readily taken up by the connective tissue cells that surround the central nervous system. So, given the right gene, our approach has application to a broad range conditions, from pain control to spinal cord injury and disorders like multiple sclerosis and Parkinson's disease."

In the study, investigators used an adenovirus--similar to a cold virus-- to deliver the beta-endorphin gene to the rat spinal cord. The virus particles were injected into the spinal fluid, where they were readily taken up by the protective sheath of connective tissue, called the pia mater, which surrounds the cord. Within 24 hours the sheath cells began secreting beta-endorphin, one of the body's natural sedatives for alleviating pain.

"The incredible simplicity and relative noninvasiveness of this approach provides a new fram
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Contact: Wayne Little
wayne.little@nih.gov
301-496-4261
NIH/National Institute of Dental and Craniofacial Research
1-May-1999