Gene Transfer Approach for FAP Desmoid Tumors Seen as Feasible

NEW YORK Jan 07, 2003 (Reuters Health) - British researchers have succeeded in transfecting fibroblasts with a normal version of the gene that when missing or mutated promotes the development of familial adenomatous polyposis (FAP) and related desmoid tumors.  This accomplishment could lead to new therapies to prevent or treat such tumors.

As the researchers note in the December issue of the British Journal of Surgery, desmoid tumors are fairly common extracolonic manifestations of FAP and an important cause of morbidity and mortality in such patients. Yet, few good treatments exist. 

Because desmoid tumors are thought to arise from the mutation or loss of the adenomatous polyposis coli (APC) gene, Dr. Rachel Hargest, from Nevill Hall Hospital in Abergavenny, UK, and colleagues hypothesized that transfecting fibroblasts, the primary cell in desmoids, with the intact APC gene might have therapeutic potential.

In the current study, Dr. Hargest"s team used liposomal transfection techniques to transfer the APC gene into fibroblasts in tissue culture and into the peritoneum of mice.

Transgene expression was observed in the tissue culture specimens up to 7 days after transfection, the authors report.  In vivo, all of the mice demonstrated transgene expression in the peritoneum and most showed expression in the small bowel mesentery, liver, and intestinal tissues.

"The present study clearly demonstrates prolonged APC transgene expression in benign mesentery and peritoneum following a single intraperitoneal treatment," the researchers state.  "Taken to its extreme, this may allow the expression of wild-type APC in preneoplastic lesions in an attempt to prevent the initial development of desmoids."

Still, "further work is needed in animal models of desmoid disease to assess the clinical effects of gene therapy," the investigators conclude.

SOURCE:

• British Journal of Surgery 2002;89:1563-1569.