SARS-CoV-2’s inflammation profile is something quite unique, immunologist Associate Professor Ashley St John realised early in February
2020. While most resources had been diverted to contain the pandemic and uncover the first building blocks — such as the genomic sequence of the virus — that would underpin subsequent discovery science, St John knew she, too, could contribute
and make a difference.
“While the initial steps were very competitive, unanswered questions would continue to challenge scientists,” says St John, who is from Duke-NUS’ Emerging Infectious Diseases Programme.
Her previous experience of applying her expertise during an outbreak — that time the Zika outbreak — had given her the confidence to take the plunge this time and investigate a familiar target: mast cells, the type of white blood cell that
is responsible for immediate allergic reactions in an unfamiliar landscape.
“That experience taught me that if you go ahead and try to contribute, it can pay off. So, my goal was to ask specific questions and establish the systems to address more questions as we learnt more about the virus.”
THE DRUG COCKTAIL TESTED CONSISTS OF TWO DRUGS, INCLUDING ONE WHOSE MAST CELL-STABILISING PROPERTIES ST JOHN BELIEVES COULD HELP TACKLE SEVERE COVID-19
Taking measured risks
St John split her focus between finding ways to make less successful vaccines work better and investigating new therapeutic options that would help reduce or avoid the inflammation that SARS-CoV-2 can trigger in the lungs by focusing on mast cells.
While mast cells are essential in clearing a pathogen, when they continue to linger on high alert, they can cause swelling and build-up of fluid, leading to laboured breathing, similar to what people with asthma experience.
“A lot of these symptoms are very similar to the respiratory distress experienced by people with COVID-19,” she explains.
And she already had a lead for a treatment option. She’d been conducting a clinical trial to assess the effectiveness of a mast cell-stabilising drug in
the management of dengue, particularly to prevent the vascular leakage triggered by severe infections.
This drug, used in the management of asthma and other allergies for more than 30 years in the United Kingdom, Europe and many countries around the world, works by preventing the inflammation — or irritation — triggered by mast cells
by blocking them.
“We think we can quieten them, help the tissue recover and prevent the coughing and laboured breathing,” explains St John of the benefit she hopes the drug could have in COVID-19 patients.
Twitter contact
With COVID-19 cases dropping rapidly in Singapore during the second part of 2020, St John was forced to look to international partners to conduct the trial. With her strong ties to Duke University, she contacted clinicians there to see whether
they would be interested in pursuing this project with her.
As she was pitching her idea, life-science start-up Sen-Jam Pharmaceutical Partners reached out to her on Twitter. They had had a similar idea and wanted to test an approved non-steroidal anti-inflammatory drug.
“They kept messaging me,” she laughs.
It wasn’t just Sen-Jam who had reached out. She had been inundated with requests. But what was key for St John was to identify the right partners whose science was sound. The support from the School’s Centre for Technology and Development (CTeD) was invaluable to her.
“The CTeD team was super supportive in helping to manage all these inquiries,” says St John, who also credits the CTeD team with brokering the successful deal with Sen-Jam that was announced today.
The partnership meant that St John’s mast cell-stabilising drug would be combined with a non-steroidal anti-inflammatory drug to tackle severe COVID-19 infections. Duke University, too, would come on board to advise on the clinical trial.
“It was really hard keeping all of this secret until all the paperwork was done,” confesses St John.
Charting her own path
And all the while, she was ready to do her media rounds, where she’d break down the latest medical news for everyone to understand — it was not only researchers who needed accurate information about the pandemic.
Serving as a role model for other young women in science was also important for St John. Women in general are underrepresented in science leadership. In this regard, St John was resilient, ensuring her efforts showed young women that research
is a rewarding path; one that a researcher can shape for themselves.
“Sometimes I just have to do my own thing,” sums up St John. “And, you know? It works out. It works out.”