Five minutes with a Pulmonary Fibrosis Researcher: Dr John Mackintosh

December 8 2020

Dr Mackintosh sat down with the PACT team to talk about his teams TELO-SCOPE trial, including how it started, what the team hopes it will achieve and the challenges they’ve faced.

Tell us a bit about yourself and why you chose PF as your research area:

I am a respiratory and lung transplant physician at The Prince Charles Hospital. Early in my clinical training I became very interested in the diagnostic challenge of interstitial lung diseases. I was very lucky to have a mentor who suggested pursuing further training at the Royal Brompton Hospital – an opportunity that I will never forget. There are so many unknowns in Pulmonary Fibrosis and interstitial lung disease and it is this which has drawn me to research. As a clinician I feel a strong sense of responsibility to translate the great scientific and research achievements in Pulmonary Fibrosis into better clinical outcomes for patients with this disease.

Describe your clinical research project in a couple of sentences:

We have recently been fortunate to receive funding from the Medical Research Futures Fund to conduct the TELO-SCOPE study, a study I am very passionate about. This is a clinical trial which will use a synthetic hormone to treat Pulmonary Fibrosis in adults and children whose disease is associated with telomere shortening.

Tell us how this project came about:

Telomeres are caps on the ends of our cell’s chromosomes which help to protect our DNA – they work a lot like the plastics caps on the end of a shoelace. Our telomeres become progressively shorter as we get older – our biological clock. Research has shown that in some people with Pulmonary Fibrosis the telomeres are abnormally short – meaning they lose their ability to protect the DNA from damage. For these people, the telomere and its shortening appears to be fundamental to their disease. It has been shown that a hormone, danazol, can help to preserve the length of telomeres. The TELO-SCOPE study will evaluate the efficacy and safety of danazol in people with pulmonary fibrosis associated with telomere shortening.

What do you hope this project will achieve?

We hope to show that it is possible to safely target a cellular pathway which we believe is fundamental to the pathogenesis of Pulmonary Fibrosis. This will help to demonstrate that people with Pulmonary Fibrosis associated with telomere shortening are a distinct group for which precision therapy might be possible.

What has been the biggest challenge of the project so far?

The trial is currently in its infancy. I’m sure that there will be many challenges to come, but at the moment it has been a great experience and a lot of fun turning a long term dream into a robust clinical trial that will be safe for participants and provide practice-informing results.

The people working on this project are:

The study is led by Dan Chambers at The Prince Charles Hospital, Tamera Corte at RPAH, Adam Jaffe at Sydney Children’s Hospital, Ian Glaspole at The Alfred, Peter Hopkins at The Prince Charles Hospital, Nicole Goh at Austin Hospital, Chris Grainge at John Hunter Hospital and Hiran Selvadurai at The Children’s Hospital Westmead. As an early career researcher I was very fortunate to be included in this established group. Our study is supported by a number of other clinicians and scientists across Australia including Hilda Pickett (Children’s Medical Research Institute), Jo Dickinson (Menzies), Jeremy Wrobel (Fiona Stanley Hospital), Paul Reynolds (Royal Adelaide Hospital), Roger Reddel (Children’s Medical Research Institute) and Stephanie Yerkovich (The Prince Charles Hospital). We have also had input from a number of international experts.

What do you see as the biggest evidence gaps in PF care? What are the clinical research priorities?

The holy grail would be treatments that reverse Pulmonary Fibrosis. Until then, we are in desperate need of treatments that stop Pulmonary Fibrosis and effective therapies for cough. Finally, we need to find ways to detect Pulmonary Fibrosis early, before symptoms present. This would go a long way to achieving better outcomes for patients who are often diagnosed too late.