New approach to gene therapy for cystic fibrosis reported by Canadian scientists

Toronto, ON December 23, 2003 Scientists funded by the Canadian Cystic Fibrosis Foundation (CCFF) today reported preliminary findings that point to a novel way of delivering gene therapy for cystic fibrosis (CF).

In a paper published in the scientific journal Proceedings of the National Academy of Sciences (PNAS), Dr Jim Hu and colleagues at Toronto’s Hospital for Sick Children described a new gene delivery vector for cystic fibrosis lung gene therapy. This vector transfers a normal gene into targeted epithelial cells, which line the airways, and produces a necessary protein (in place of the protein that is defective in CF). It may also have a positive, therapeutic effect in combatting a type of chronic lung infection which, in cystic fibrosis, can be life threatening.

“The findings do not constitute a quick solution to the problems in cystic fibrosis,” says Dr Hu. “But we are very excited; this is definitely a step in the right direction.”

One of the challenges in gene therapy studies is to deliver and express the normal gene in the targeted cell type efficiently and without provoking an immune response. The new vector, developed by Dr Hu, has apparent advantages over other vectors for use in lung gene therapy for cystic fibrosis.

The vector features control elements that direct the gene to the cells of interest, and once delivered, it seems to produce a relatively low inflammatory response. This work by the Toronto team also appears to be the first published study using a CF mouse model to demonstrate a therapeutic effect in reducing chronic and severe lung infection in cystic fibrosis, caused by a deadly strain of bacteria, known as Burkholderia cepacia complex.

“This is very encouraging work,” says Cathleen Morrison, chief executive officer, Canadian Cystic Fibrosis Foundation. “Of special interest to individuals with cystic fibrosis is the potential, which Dr Hu and his team have demonstrated, of reducing chronic CF lung infection through gene therapy.”

Dr Hu has held a scholarship award from the Canadian Cystic Fibrosis Foundation since 2000, and has received research funding since 1996. The above investigations have been supported through grants and awards from the CCFF, including funds from the Foundation’s special program in applied research and therapy (SPARX).

A summary of this work by Jim Hu et al of Toronto’s Hospital for Sick Children appeared in the December 23, 2003 issue of PNAS. The article is entitled “Protection of Cftr knockout mice from acute lung infections by a helper-dependent adenoviral vector expressing Cftr in airway epithelia”.