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Gene therapy for ulcerations of the gastrointestinal tract.

Ulcer healing requires cell proliferation, migration (re-epithelialization) and angiogenesis - all ultimately leading to scar formation. All these processes are controlled by growth factors. Gene therapy has shown only limited promise for effective treatment of congenital diseases. This is due to time-limited gene expression, adverse immune responses and/or complications related to viral vectors. However, short- term expression of genes encoding angiogenic growth factors appears to be ideal for treatment of chronic ulcers and wounds, which require only limited temporal gene overexpression. Since angiogenesis is essential for wound and ulcer healing, the genes encoding proangiogenic growth factors have been utilized for treatment of experimental esophageal, gastric and duodenal ulcers. These studies demonstrated that a single local injection of plasmids expressing vascular endothelial growth factor and angiopoietin-1 dramatically accelerates the healing of duodenal, gastric and esophageal gastric ulcers. Preliminary data indicate that such treatment can also be effective for the healing of experimental colitis.