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Naked DNA Rejuvenates Rheumatoid Rodents

Scientists have unveiled a stripped-down form of gene therapy to treat arthritis in an experimental animal model. Naked DNA, unencumbered by the standard assortment of gene carriers, was effective when injected directly into muscle tissue. Remarkably, this straightforward procedure dramatically reduced chronic arthritis symptoms in the joints, and now offers an innovative approach for eventually treating human disease. The results of the study, carried out at NIDR, appeared in the June 15 issue of the Journal of Clinical Investigation.

The naked DNA consists of a double-stranded circle of nucleotide bases, known as a plasmid. This particular plasmid contains the genetic code for human transforming growth factor-beta (TGF-), a protein that is a key regulator of inflammation -- the body's response to infection or tissue damage.

Dr. Xaio-yu Song of NIDR

Drs. Xaio-yu Song and Sharon Wahl from NIDR, and MiLi Gu from the Food and Drug Administration tested the TGF- plasmid in a rat model for human rheumatoid arthritis. In this model, animals that are injected in the abdomen with a preparation of bacterial cell walls soon develop swollen and inflamed joints in the feet. The acute arthritic phase lasts several days and then develops into a long-term chronic condition that is marked by the erosion of cartilage and bone within the joints.

When the scientists injected TGF- plasmids into muscle tissue, they noticed a dramatic reduction in disease symptoms in the joints. The number of affected joints and the amount of swelling in the joints were both substantially reduced. Although injection of plasmids prior to initiating arthritis with bacterial cell walls did not prevent the onset of disease, injections timed at different periods after symptoms began alleviated conditions in the later occurring chronic phase. Inflammation was greatly reduced and essentially no cartilage or bone destruction occurred. Not only does the procedure avoid the invasion of painful joints, but also a single injection into muscle suppressed arthritis symptoms for up to 3 months after treatment.

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