Although there are no effective drugs for severe influenza, a breakthrough led by Associate Professor Michelle Tate, in collaboration with Associate Professor Ashley Mansell, has led to innovative treatments that target the body rather than the virus itself to limit inflammation and ultimately save lives.
In Australia, yearly hospitalisations and deaths from influenza have risen over the last decade to an estimated 18,000 and 3,500, respectively[1]. In many fatal cases, it is not just the virus that causes harm, but the body’s immune system launching an extreme inflammatory response, sometimes called a ‘cytokine storm’, that damages the lungs and other organs.
There are currently no targeted treatments for this storm and no widely approved therapy that can precisely calm the overactive immune response driving severe lung damage.
Fascinated by the intricacies that make up the immune system, Associate Professor Tate has dedicated her career to understanding the processes by which viral infections cause disease and identifying novel targeted therapies.
The immune system’s effectiveness depends on finding a critical balance between having some inflammation to fight infection, but not in such excess that it leads to life-threatening disease. Now more than ever, in a post COVID-19 society, the devasting impact of respiratory viruses has been unmistakably clear, highlighting the need for proactive interventions to prepare for future pandemics.
Associate Professors Tate and Mansell’s project focused on understanding and mitigating the excessive inflammation that drives severe, adverse influenza outcomes. Their project discovered how the host’s NLRP3 inflammasome[2] contributes to hyperinflammation in the lungs during severe influenza infection, helping to shape new directions in the field. It also led to the development and patenting, in partnership with industry, of a novel inflammasome inhibitor that reduces pulmonary inflammation.
‘All the major discoveries in medicine have come from basic research. It's the foundation of understanding the immune system and how we can modulate it with drugs. That’s what we did – we took a basic discovery in the lab and then we were able to apply that through industry and make a novel drug.’ said Associate Professor Tate.
The drug’s dual targeting capability opens new avenues for treating a range of inflammatory and infectious diseases, including silicosis and COVID-19 related lung injury.
Developing this drug during the actual COVID-19 pandemic was nothing short of a challenge for Associate Professor Tate who, as a virologist, was working harder than ever. On a positive note, industry partners responded positively, recognising that pandemics happen and are not something of the past.
Associate Professor Tate credits the impact of her research to having the opportunity to collaborate with other researchers around her and bringing together a broad depth of expertise to solve this problem.
Anyone can get the flu which means anyone can get seriously unwell from it. This new drug provides hope for patients diagnosed with not just influenza infections, but other respiratory diseases where inflammation is the issue.
Next steps
Associate Professor Tate will continue to explore the potential use of inhibitors to treat other diseases. By continuing to investigate biomarkers that identify patients at risk of hyperinflammation, Associate Professor Tate aims to reduce hospitalisations, prevent deaths, and improve recovery outcomes for Australians affected by respiratory infections. To do so, she will continue to collaborate with industry to ensure rapid translation of discoveries into clinical practice. This work represents a critical step toward transforming how we treat respiratory infections in the future.
Chief investigator: Associate Professor Michelle Tate
Institution: Hudson Institute of Medical Research & Monash University
Team members:
- Associate Professor Ashley Mansell
Grant: Ideas Grants
Year: 2019–2022
Funding amount: $597,286
[1] Australian Centre for Disease Control. Season flu (seasonal influenza). Available from: Seasonal flu (seasonal influenza) | Australian Centre for Disease Control
[2] An inflammasome is a multimolecular protein complex that acts as a sensor in the immune system and detects danger signals such as infection or stress from damaged cells and pathogens.