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.”
Source: Gastroenterology 2004;126:1122-1133,1199-1201. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Therapy: Disease Models, Animal: Genetic Engineering: Genetic Techniques: Liver Cirrhosis, Experimental: Investigative Techniques: Therapeutics: Gene Therapy: Collagenases: Matrix Metalloproteinases: Neutrophil Collagenase: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
