From remarkable patients to remarkable cures

How Australian research is leading to new treatments

Some patients make an indelible impression. For Professor Russell Dale, the catalyst was a child with Acute Disseminated Encephalomyelitis (ADEM), caused by brain inflammation. “These children are unconscious and they’re often brought to the Intensive Care Unit, where you give them high dose steroids,” he explains.

Within five days, the patient was walking again. “It was quite a remarkable thing to treat,” he says. Today, Dale is Professor of Paediatric Neurology at the University of Sydney, researching interactions between the immune system, inflammation and the brain.

For Professor Adam Jaffe, it was a 14-year-old boy with cystic fibrosis.

“He was very sick, but he was the sole carer for his mum, who had multiple sclerosis and was in a wheelchair,” says Jaffe. “He died a couple of years later.”

Today, Jaffe is a Paediatric Respiratory Consultant at Sydney Children’s Hospital, the John Beveridge Professor and Head of Paediatrics at the University of New South Wales (UNSW) and an advocate for patients with rare diseases.

For both, the question is how to balance clinical work and research.  “To me, embedding research into healthcare delivery is a fantastic advantage of the job that I do,” says Jaffe. “It’s an opportunity for clinicians to see a problem in their day-to-day clinical work and fix it.”

How research informs treatment

Shafagh Waters PhD, the Group Leader of the Molecular and Integrative Cystic Fibrosis (miCF) Research Centre at the Sydney Children’s Hospital and UNSW, agrees. She works with Jaffe on precision medicine; finding a way to match individual cystic fibrosis patients with the right drug for them. “We don’t all respond the same way to drugs,” she says.

Working in a lab in close proximity to a hospital makes it easier to recruit research subjects, as Waters can speak to parents at the hospital’s regular cystic fibrosis clinics. “We present it as a research study, and we ask anyone who is going to be part of it not to expect to benefit from it directly,” she says, adding she wants to see the research “bear fruit and actually help the patients”.

Waters uses tissue-specific endogenous stem cells, gathered from the nose, to create patient ‘avatars’, or mini lungs, on which drugs are tested. “The choice of drug that the patient will be given is going to be informed by the result that we got from the mini lung of that individual,” she says.

There’s no doubt that combining research and clinical practice bears fruit, but it can be so effective that it propels the research beyond the bounds of Australia’s slow-moving regulatory environment.

If a drug is matched to a patient with a very rare genetic profile, for example, there can be a problem. If only a few people need a drug, the cost per patient can soar; the Pharmaceutical Benefits Scheme will also need evidence it will substantially increase life expectancy before they can authorise it. Unfortunately, in the case of very rare diseases, there aren’t enough patients to take part in a clinical trial to produce such evidence.

“We’ve got various regulatory bodies, but they struggle to address the rapidly changing field of new drugs, technologies and precision medicine,” says Jaffe. “What we need to do is create a regulatory environment that accelerates treatments from the development to access to patients.”

Then there’s that other chronic obstacle: lack of funding. “It’s a critical problem,” says Jaffe.

But sometimes, with the right combination of persistence, storytelling and collaboration, it’s possible to overcome the challenges. In 2020, Jaffe and colleagues supported Rare Voices Australia, the national peak body for Australians living with rare diseases, in writing the National Strategic Action Plan for Rare Diseases. Launched by the Hon Greg Hunt, the former Minister for Health and Aged Care, the Plan outlines the principles and actions to bring about the best health and wellbeing outcomes for Australians living with a rare disease. They were successful – UNSW was recently awarded $1.9 million in federal funding for the Rare Awareness, Education, Support and Training (RArEST) project, to develop and deliver resources and training.

The framework

Dale’s approach to integrating medicine and research was to do a PhD, to better understand research methodology. “My clinical research has been about defining syndromes,” he says. “Being a clinician is very important, because otherwise I wouldn’t be able to identify clinical problems.”

He says that good research outcomes arise not just from good experimental design, but also from a “health system that is agile enough to encourage research, with the infrastructure to support it”. The marriage of hospitals and universities in NSW means there are doctors who identify problems, and scientists who can help structure the research. “The meeting of universities and hospitals is incredibly important,” says Dale.

He says it’s very hard for clinicians caught in the everyday stresses of work to collect data in a systematic way. It’s even harder if they aren’t in near contact with scientific laboratories, because they miss out on the meeting of minds. “You discuss things as a group,” says Dale. “A scientist can tell you whether something is possible, or about experimental techniques.”

He adds that, thanks to the work of statisticians and data analysts, the nature of randomised clinical trials is changing. Previously, a trial protocol demanded two groups of patients, some of whom received the treatment and some of whom didn’t. “That still happens,” says Dale, “but there’s far more complex methodology now. You can stop a trial halfway through if it’s already proved what needs to be proven.”

If a drug proves itself – and sometimes drugs can show results very quickly – then researchers no longer withhold it from the other cohort.

All three researchers expressed concerns that too many “safe” trials, where the outcomes could be predicted, were being funded over riskier research that might have a more significant outcome.

Yet, says Dale, “Australia clearly punches above its weight – the medical research is highly competitive with North America and Europe.” He says he thinks it’s because of Australia’s integrated public health system. “In Australia, I think it empowers research.”