Neonatal Paediatrician Dr Marcel Nold, Consultant at Monash Children’s Hospital is conducting research on how the microbiome interacts with the immune system and the impact of such interactions on long-term health of newborns.
This includes a recently published systematic review on the impact of microorganisms colonising newborns’ lungs, a clinical trial using the drug anakinra to prevent inflammation in preterm babies, and an ongoing study, GLAM & I, which aims to understand the development of the immune system and the microbiome in 500 babies, children and adolescents.
“What I really want to do is quality research that ultimately makes a difference to the lives of my patients and their families.”
And that is exactly what Dr Nold is doing. In the quest to understand how microbiome and immune system interact, multiple studies are underway to answer the question from different aspects.
Systematic review
The Monash Children’s Hospital consultant was one of the lead authors for a recently published review of primary research to study the impact on the maturing immune system when microorganisms from the outside environment colonise the lungs in newborn babies and children.
Dr Nold, who is also Professor of Paediatric Immunology within the School of Clinical Sciences at Monash University, and Group Head at the Hudson Institute of Medical Research, is one of the lead authors and works with an interdisciplinary team from Hudson Institute and Monash University.
The findings of the systematic review are a precursor to the study “The Gut, Lung and their Microbiomes & Immunology”, or GLAM & I for short. It aims to understand how the immune system evolves and how the microbiome colonises the body, and particularly the lungs.
It also looks at how this colonisation is different between health and disease, and how the immune system and this colonisation influence each other.
“It is a big challenge to try and understand all of this. And GLAM & I is a very big study. Essentially, this review helps the readers to understand where we are today, with a specific focus on one area that we understand even less than other areas, namely the lung microbiome,” the clinician-scientist says.
The anakinra pilot clinical trial
Professor Nold, whose research group at the Hudson Institute focuses on “Interventional Immunology in Early Life Diseases and Beyond”, explains that pre-term babies often get a lung disease called bronchopulmonary dysplasia (BPD), sometimes called neonatal chronic lung disease.
“We identified that a protein called interleukin-1 or IL-1 is one of the ‘bad guys’, so to speak. If there is too much IL-1, it can wreak havoc in the baby’s lungs, brains and other organs,” he says.
Professor Nold says that anakinra, a drug already on the market, can target IL-1 to stop its effects on inflammation.
Anakinra has been used in about 200,000 patients over the last 20 years, but never in preterm babies. “So our idea was, could we trial Anakinra in preterm babies to prevent this inflammation and thereby prevent disease. And – over a long journey – that’s exactly what we did.”
Professor Nold says not only is this the first trial ever to use this drug in preterm babies, it’s the first time the drug has been trialed as a targeted anti-inflammatory therapy in preterm babies.
The number of participants of such ‘first-in-population’ trials is usually small, because one of the first goals has to be to establish safety. This is no different for Anakinra Pilot.
The trial is ongoing, and the team has so far recruited 17 out of a target of 24 preterm babies. “We still have 7 babies to go, so we can’t make any final statements yet. But the 16 babies who have completed the treatment course have tolerated anakinra very well,” Professor Nold says. “Also, Starship Hospital in Auckland, New Zealand, will join our trial in July. This is another exciting development, because it will show that anakinra is safe not only in our unit and in Australia, but in another country as well.”
He is hopeful that the clinical trial can conclude by the end of 2023 with definitive findings.
The babies who are recruited in Anakinra Pilot will also go in the larger, and longer-term GLAM & I study. Professor Nold and his team will thereby be able to see how the drug affects the developing immune system and microbiome. At the same time, he and his team can compare babies who have received the drug with those who did not.
The Gut, Lung and Microbiome and Immunology (GLAM & I) study
Professor Nold’s team will follow up with their participants for up to 12 years.
The study began in 2020 and the target is to recruit 500 babies. So far, about 100 have been recruited.
Professor Nold, who undertook his paediatric training in Germany and spent three years doing research in Denver, United States, moved to Melbourne in 2009 with his wife, Professor Claudia Nold, to set up their laboratory, which played a big part in this study.
He describes Claudia and himself as basic immunologists with a strong interest in anti-inflammatory cytokines and in the development of drugs that mimic cytokines’ functions.
Professor Nold says that once we have a better understanding of how the immune system works, we could develop drugs to target the problematic mediators – just as he and his team have done with IL-1.
As for the microbiome, he says first new microbiota-based therapies are emerging, but there is lots more to come. He adds that advancing knowledge in this field will open the door to a world of therapeutic opportunities.
Strategic partnerships
This is where the partnership between Monash Health and the Hudson Institute is crucial.
“We’re really fortunate to have a collaborator here at the Hudson Institute, Associate Professor Sam Forster, who is one of the few scientists who has considerably sharper tools than most others worldwide to investigate the microbiome – and one of those sharper tools is bacterial culturing.
“For example, most researchers would put the bacteria through what’s called sequencing to understand which scientific class they belong to. But sequencing doesn’t tell you whether these bacteria were alive and what their functions are. With culturing, you can do just that,” Professor Nold explained.
In other words, they can not only differentiate between “good and bad” bacteria, but also learn how good bacteria function, and then either mimic that or take those bacteria, grow them, and give them back to patients.
Professor Nold acknowledged that this multi-faceted research is a mammoth task, which is only possible because of the strategic partnership between a hospital, a research institute and a university.
“The fantastic teamwork enabled by this campus and its people on the wards and in the labs makes such an ambitious study possible. We are very fortunate to be here, all working hand in hand, and I don’t know many other places where we could do this,” he says.
“And of course, we are all extremely grateful to the families and their children who are saying yes to this research – it is a big investment in the future.”
“Living the dream”
“I’m essentially doing what I’ve always wanted to do, which is work in medicine and science at the same time, really bringing those two together,” Professor Nold says.
“This allows me to work towards my overarching goal, which is to do quality research that ultimately makes a difference to the lives of my patients and their families.”
Meet the team
Professor Nold’s team consists of:
Co-lab head: Prof Claudia Nold
Postdoctoral research fellows: Dr Ina Rudloff, Dr Steven Cho
Lab manager: Esteban Pinto
Research nurse: Rebecka Atkinson
PhD students: Dr Elly Green, Sara di Simone, Josephine Owen, Holly Ung, Steven Garrick, Briana Peterson
RACP advanced trainees: Dr Emma Turton, Dr Nadia Truong (also affiliated with Hudson Institute of Medical Research)
Honours students: Abby Boppana
His team also has joint lab operations with Dr Rimma Goldberg, who is a consultant gastroenterologist at Monash Health and also has an appointment at Monash University.
Her lab comprises:
Research assistants: Marie Lee, Indiana Zorkau
PhD student: Dr Ralley Prentice