What are some of the key findings, progress and discoveries you have made with your research to date – and how will this make a difference to patients with this disease?
Our research has mostly focussed on COPD, with further projects underway in severe asthma, bronchiectasis in children, and cystic fibrosis. We have shown that failed airway macrophage phagocytic function, with pro-inflammatory consequences, is a common finding in all of these chronic inflammatory lung diseases. We showed that mechanisms for these defects include changes to the sphingosine-signalling pathway, and showed in two clinical trials that the macrolide antibiotic Azithromycin could significantly reverse the phagocytic defects. Despite this exciting data with Azithromycin, we and others have shown that treatment is potentially accompanied by an increase in the carriage of Azithromycin-resistant bacteria. In collaboration with Gilead Sciences USA, we are therefore investigating two Azithromycin-based molecules with weakened or no antibiotic properties. Both agents retain their anti-inflammatory properties, improve the defects in sphingosine signalling and improve macrophage phagocytic function in vitro, and are now being tested in our smoke-exposed emphysema mouse model. Our most recent studies are further investigating a new therapeutic strategy using our recently discovered MP-A08 sphingosine pathway modulator to target the sphingosine pathway and the defective macrophage function and inflammation in COPD.
What do you hope to achieve with this research project?
We aim to advance the knowledge in the field of COPD and other chronic inflammatory lung disease. Ultimately, we want to put forward a lead candidate for phase I/II trials of a new therapy that can modify/correct dysfunctional sphingosine signalling in COPD with clinical significance.
How important was the funding from Lung Foundation Australia to your work?
Our enthusiastic and dedicated team of researchers are completely funded by competitive grants and awards, so our work could not progress if these funds were not available. My own career progression was largely due to me receiving the Lung Foundation Australia/Boehringer Ingelheim Research Fellowship in 2003.
Do you have a message for Lung Foundation Australia’s supporters?
The value of your support of Lung Foundation Australia is immeasurable. The careers of many talented respiratory researchers are completely dependent on competitive grants and awards such as the ones offered by Lung Foundation Australia. Without this support, many of these researchers would not be in a position to progress their careers, and our road to developing new therapeutic options for our patients would be severely hindered.