Correction and measurement of the basic defects in cystic fibrosis [ 2007 - 2009 ]

Research Grant

Brief description Airway disease caused by the genetic disease cystic fibrosis (CF) cannot currently be prevented or cured. Current treatments (other than lung transplant) can only slow the inevitable decline in lung health. Early death from lung failure occurs for many with CF. We have developed a gene transfer technique to introduce the corrective gene (CFTR) into CF-diseased airway cells. We have used airways in mice to test and develop this method, to determine if long-lasting genetic correction of the airway cells can be achieved. The gene is introduced into the airway as a single small dose of special delivery-particles (vector) that have been built using highly-modified components of the HIV-1 virus. If ultimately successful in humans with CF, the disease should be halted, or even cured. Our recent work indicates that we have been able to insert the gene into airway progenitor cells, confirming our hypothesis that long-lasting gene expression can be achieved this way. To know if the method would be safe and effective in humans, we must now test the technique in sheep (as a human-size lung) and in marmosets (as a human-like lung) before clinical trials could be considered. We will monitor animals for up to 3 years to be sure the effect of the gene is truly long-lasting, and we will document how the gene-transfer vector disappears from the body. We have also discovered a new way to examine the detail of the very thin fluid layer on the airway surface. This fluid is too shallow in CF airway (allowing bacteria to stick and start disease) and so a successful gene therapy should return the fluid to it's proper depth. This method uses X-ray light from a synchrotron, and we expect it will work without the need to sacrifice animals to measure the airway surface. If successful it also has potential to be used much like a normal X-ray in humans with CF, to test if a gene therapy has worked.

Funding Amount $AUD 929,335.70

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant