Breathe easier – Nature-inspired treatments could ease acute respiratory distress

By Barbara Pinho

In 2014, Professor Kai Zacharowski, director of the Clinic for Anaesthesiology, Intensive Care Medicine and Pain Management at Goethe University Hospital in Frankfurt, Germany, was treating a particularly complicated case of an Ebola patient in acute respiratory distress.

As the man’s condition worsened, Zacharowski turned to an experimental new drug – a molecule naturally present in the human body (FX06) – He hoped it might stabilize the patient. The procedure worked. An outcome that was both professionally inspiring and personally fulfilling.

“We were able to save the life of a human being, a father and a colleague,” Zacharowski said.

Link to the pandemic

This experience came back to Zacharowski’s mind a few years later, when the Covid-19 pandemic broke out. His department at the hospital was responsible for treating the largest number of Covid-19 patients in the Hesse region of Germany.

With EU funding, a large-scale research effort involving several countries has been set up to try to understand how this same treatment could be used to prevent Covid infection from progressing to its most severe and deadly form: acute respiratory distress syndrome (ARDS).

The COVend project, led by Zacharowski, began in the midst of the pandemic in November 2021. The researchers decided to harness the power of artificial intelligence (AI) and systems biology to better understand how FX06 works in individual patients and determine its therapeutic value as an effective drug, with no known side effects, to use in the fight against Covid-19.

“We are optimistic that our research will provide unprecedented insights into ARDS,” Zacharowski said.

A wider scope

But the research team’s mission didn’t stop there. While COVID-19 has brought attention to this very scary disease, it can be triggered by a variety of factors, including bacterial or viral infection, sepsis, trauma, surgery, or blood transfusion. It can also be caused by inhaling toxic vapors or liquids.

There is currently no effective treatment for ARDS, which is a difficult condition to manage in intensive care units. COVend researchers estimate that there are between 30,000 and 120,000 cases of ARDS each year in the EU, and that the syndrome accounts for around 10% of all intensive care admissions. It also has a very high in-hospital mortality rate of up to 45%.

Acute respiratory distress occurs when fluid builds up in a patient’s lung air sacs, preventing them from filling properly with air and preventing oxygen from entering the body, often with fatal consequences. Patients who survive often suffer permanent scarring of their lungs.

“ARDS is a devastating disease that not only has a high mortality rate, but also results in a long recovery for many survivors,” Zacharowski said.

Natural protection

FX06 is a naturally occurring protein fragment in the human body that binds to cells that line blood vessels, helping to protect them. The drug may potentially reduce the mechanical cause of ARDS, when fluid from very small blood vessels leaks into surrounding tissues, including the alveoli.

“

ARDS is a devastating disease that not only carries a high mortality rate, but also results in a long recovery for many survivors.

Professor Kai Zacharowski, COVend

The COVend research team has successfully implemented the first clinical trial on the use of FX06 in mild and moderate ARDS. It is currently recruiting approximately 260 patients in France, Germany, Lithuania, Romania and Spain. Results are expected in early to mid-2026.

The goal is to identify patients who will benefit most from treatment with FX06. To do this, the COVend team profiled hundreds of molecules in patients’ blood and used AI to study their role in disease progression.

“It’s a fascinating molecule because it can be used in many ways,” says Dr. Petra Wülfroth, COVend Innovation Manager and Chief Scientific Officer at F4 Pharma, an Austrian biopharmaceutical company partnering in the project.

The research could also prove useful for possible future pandemics, as the treatment targets a disease that could be triggered by a range of different pathogens.

“My dream would be to see this molecule used in intensive care whenever the permeability of small blood vessels is increased – a potentially fatal situation.”

Breathe like a bird – or a fish

Currently, in the absence of effective pharmaceutical intervention, patients with ARDS are often given oxygen or placed on a ventilator to help them breathe. In severe cases, their blood can be oxygenated outside their body using a technique called extracorporeal membrane oxygenation (ECMO).

However, these treatments can have serious side effects for the patient. ECMO carries a risk of infection or clotting, while prolonged use of a ventilator can damage lung tissue.

Professor Margit Gföhler, who teaches biomechanics and rehabilitation engineering at the Technical University of Vienna (TU Wien) in Austria, is leading an EU-funded project called BioMembrOS that will run for three and a half years until mid-2027.

“

Nature has bioengineered the most effective solutions to life’s challenges.

Professor Margit Gföhler, BioMembrOS

Together with his TU Wien colleague Michael Harasek, a specialist in chemical engineering and membrane science, they are coordinating an international research effort to develop an alternative respiratory support device inspired by the natural and highly efficient respiratory mechanisms of fish and birds.

“We need completely different approaches if we want to develop new respiratory support devices that don’t have the problems we see with current options,” she said.

When we breathe, oxygen passes from the lungs into the bloodstream via the alveoli and a network of tiny blood vessels called capillaries. At the same time, carbon dioxide passes from the blood into the lungs to be expelled from the body as we exhale.

This process is known as gas exchange. It is severely compromised in ARDS when the alveoli are flooded. Gas exchange allows the body to replenish oxygen and remove carbon dioxide, both of which are necessary for survival.

New membrane

The BioMebrOS team, which includes researchers from Austria, Germany, Italy, Portugal and South Africa, is working to develop a new membrane structure based on the structural design of bird lungs, which exchange gases more efficiently than those of mammals. They will also incorporate aspects of fish gill respiration, including their superficial contact with fluids.

The idea is to create a device with a membrane that removes carbon dioxide from the patient’s blood as it passes through it and infuses it with oxygen.

“Nature has developed effective bioengineered solutions to life’s challenges,” Gföhler said. “By adopting the structural and functional features of the most advanced gas exchangers, we will create a radically improved technology.”

The first goal of BioMembrOS researchers is to develop a small testable prototype of this membrane structure and to test its effectiveness in in vitro blood tests.

“The overall goal for the future would be to make it so efficient and so small that we could implant it into the patient,” said Gföhler, who hopes devices incorporating their membranes will be available to patients within the next decade.

The Covid-19 pandemic may have helped to focus public attention on the enormous suffering caused by ARDS, but the challenge is much broader. ARDS affects a large number of patients worldwide, and respiratory diseases are the third leading cause of death in the EU.

Whether it’s through research into new molecular drugs or improving the way we build medical ventilators, more research is needed to reduce the distress caused to patients around the world. Nature could prove an important ally.

The research presented in this article was funded by the EU Horizon programme, including, in the case of BioMembrOS, through the European Innovation Council (EIC). The views of the interviewees do not necessarily reflect those of the European Commission. If you liked this article, please consider sharing it on social media.

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This article was originally published in Horizon, the EU’s research and innovation magazine. with Creative Commons license

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