The medical team behind a world-first trial aimed at treating premature babies with chronic lung disease have a Monash Health Award under their belts – and praise from the worldwide neonatal health community. But, for them, it’s all about what happens next.
The trial came after 10 years’ research by Monash University’s School of Clinical Sciences, Hudson Institute of Medical Research, and the Monash Children’s Hospital. The research was led by Professor Euan Wallace with neonatologist Dr Atul Malhotra and Dr Rebecca Lim, deputy head of the Hudson Institute’s Ritchie Centre, where she leads the regenerative medicine and cellular therapies unit.
Professor Wallace is the Carl Wood Professor and head of Monash’s Department of Obstetrics and Gynaecology. He says the research is a genuine breakthrough. “All too often in medical research we hear about ‘breakthroughs’ when there hasn't really been one,” he says. “This is different.”
He and Dr Lim worked on the project for 10 years; Dr Malhotra joined seven years ago. The trial was conducted in six premature babies with chronic lung disease, or bronchopulmonary dysplasia (BPD). They were all born at 24 to 28 weeks and the parents gave permission to the team for their babies to receive intravenous doses of stem cells from healthy placentas, a potential future treatment or cure.
This first phase of trial wasn’t aimed at curing or treating the potentially fatal lung condition, but to establish whether it was safe to use the placental cells in babies. It was the first time in the world that the stem cells have been trialled in this way on babies – who also happened to be premature and fragile.
The next phase, which has already begun, involves giving the same stem cells to younger babies to prevent the lung disease. So far, one baby has been given the cells; the team will trial 24. They will also give escalating doses of cells to babies who are at risk of developing the disease rather than those already stricken by it.
“We’re carefully increasing the dose of the cells that we give babies to reach a dose that we think – based on our pre-clinical experiments – will be effective as a treatment,” says Professor Wallace. “This next step is still a safety trial, but we’re giving the cells within the first 14 days of life and so, fingers crossed, we’ll see some preventative [treatment] effects.”
“All too often in medical research we hear about ‘breakthroughs’ when there hasn't really been one. This is different.”
By the end of next year the team hopes to establish that the stem cell treatment can be beneficial to premature babies with the disease. Currently, about eight per cent of babies born in Australia each year are premature, and two per cent of those – about 4000 babies a year – are at risk of developing the disease. Around 1000 a year actually do develop it.
“That might not look like a lot,” says Dr Malhotra, “but most of them require significant support in the hospital and then at home, including using oxygen at home. They can be very prone to infections and frequently get readmitted. Basically, their lung development is stopped in time, so while BPD impacts the lungs, the whole body is affected, including the brain.” Many BPD infants are at risk of developing cerebral palsy.
Effective treatment will be readily embraced by families. However, it could be argued phase one of the trial – to determine safety – was the bravest and most innovative step.
“It took a lot of courage from the families, but also from the research team,” says Dr Malhotra.
The therapy had already gone through an exhaustive period of pre-clinical trials. The fact they went from there straight into human babies turned medical convention upside-down – usually, when research is translated into medicine, it’s first trialled in adults.
“We had to convince our colleagues and those looking at the ethics of the trial that first-time use in a baby would be OK,” says Dr Malhotra. “We said, ‘We know this will cause no harm, we need to test it in the baby. Otherwise it will take us another two years to get to the baby, and it’s taken 10 years already.’”
The science is within the placenta, and the amniotic sac that surrounds the baby during pregnancy. Previous studies have shown that the human amnion has been an effective wound dressing, with healing properties. It’s been used as a wound healer since the early 1900s. When a baby’s lungs are stunted – by the disease, but also potentially by steroids used in hospital care – the growth of new blood vessels and air sacs slows. But once given stem cells from a healthy placenta, the process is kick-started.
The mother’s placenta isn’t used to harvest the stem cells. This is because premature birth is usually the result of a complicated pregnancy. The cells, then, are foreign to the baby. The key questions leading into phase one of the trial, says Dr Malhotra, were: “Is it safe to administer cells from someone else’s placenta into these babies? Will it be safe? We knew it should be, but there were still unknowns.”
The team has undertaken follow-ups every few months with the premature babies they used in the trial, successfully establishing safety.