Science

MMP-8 gene delivery quells cirrhosis in rats

Last Updated: 2004-04-13 15:36:10 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Adenoviral administration of a gene coding for human metalloproteinase (MMP)-8 helps ameliorate the cirrhotic process in rats with experimental cirrhosis, researchers from Mexico and the US report in the April issue of Gastroenterology.

Dr. Juan Armendariz-Borunda of the University of Guadalajara and colleagues note that in the rat livers, MMPs can cause degradation of extracellular matrix proteins and release hepatic growth factors. The reduction in fibrosis frees up space for hepatic cell proliferation.

The researchers employed this approach in two experimental cirrhosis models in rats. This involved a single intravenous injection of a first-generation recombinant adenoviral vector carrying a gene for human MMP-8.

The MMP-8 treatment, say the investigators, "reversed extensive liver fibrosis, stimulated liver cell proliferation and resulted in stabilized functional hepatic tests and the disappearance of abnormal gastric circulation and ascites."

In particular, after 14 days, 8 of 10 treated rats showed a hepatic fibrosis resolution of up to 60%.

Given these findings, the team concludes that "therapy with the MMP-8 gene holds promise for use in a clinical setting."

Dr. John P. Iredale of the University of Southampton, UK, in an accompanying editorial, observes that a greater understanding of related effects is essential before moving to clinical applications.

Nevertheless, he points out that this and other studies "have ensured that manipulating matrix degradation is now firmly on the map as a possible therapy for liver fibrosis."

Gastroenterology 2004;126:1122-1133,1199-1201.