Preclinical studies of gene transfer for the treatment of desmoid disease in familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) arises following mutation or loss of the adenomatous polyposis coli (APC) gene. Desmoid tumours are proliferations of fibroblasts and occur as an extracolonic manifestation of FAP. They are a leading cause of death after colectomy. The aim of this study was to assess the potential for APC gene transfer into fibroblasts in vitro and in vivo as a basis for consideration of gene therapy in the prevention or treatment of desmoid tumours.
METHODS: The APC gene was transferred by lipofection into fibroblasts in tissue culture and into peritoneum and small bowel mesentery in vivo. Reverse transcriptase-polymerase chain reaction was used to determine whether or not transfection was successful.
RESULTS: Transgene expression was recorded in vitro to 7 days after transfection. High levels of transgene expression were also seen in samples of peritoneum (all eight mice), small bowel mesentery (seven of eight), liver (seven of eight) and intestinal tissues (five to six of eight) following intraperitoneal treatment. Interestingly, transgene expression in gonadal tissues was occasionally noted.
CONCLUSION: Liposomal transfection of APC gave prolonged high-level expression of the transgene, an important basis for gene therapy. No adverse effects were recorded. Further work is needed in animal models of desmoid disease to assess the clinical effects of gene therapy.