Using precision mini-lungs to find better treatments for NTM infections

Project Duration – 2 years

What is the research about?

Non-tuberculous mycobacterial (NTM) infections are an increasingly important challenge for people with cystic fibrosis (CF), particularly infections caused by Mycobacterium abscessus (M. abscessus).

These infections can be extremely difficult to treat. Treatment often involves several antibiotics taken over long periods, sometimes including intravenous medicines, with significant side effects and limited success. There is an urgent need to find treatments that are more effective and less burdensome.

A team at the Murdoch Children’s Research Institute is screening more than 4,200 medicines, to identify those which have activity against M. abscessus. This research will take the next step by testing identified potential treatments using advanced stem cell-derived models, including precision mini-lungs.

These bacteria can survive inside macrophages, a type of immune cell that normally helps the body fight infection. By testing medicines in models that recreate interactions between M. abscessus and immune cells, the researchers can investigate how well potential treatments work in a more realistic system

The team will use models made from cells with and without CF-causing genetic changes to investigate promising medicines in a lung environment that more closely reflects the disease.

Why does this matter for people with CF?

NTM infections like M. abscessus are especially difficult to treat and can cause rapid loss of lung function. Current treatment success rates are often below 50%, while treatment can involve months of complex antibiotic therapy, hospital visits and significant side effects.

This creates a substantial physical and emotional burden for people with CF and their families. When treatment does not work, infection can continue to damage the lungs and increase the risk of severe disease requiring lung transplantation.

By identifying more effective drug combinations before they are tested in people, the researchers aim to improve treatment success, reduce unnecessary exposure to toxic antibiotics and preserve lung function.

What will the research do?

The research team will:

• Test promising medicines against M. abscessus using human stem cell-derived models that recreate interactions between the bacteria and lung immune cells.
• Test the priority medicines against a range of M. abscessus strains collected from people with CF to understand whether their effectiveness varies between bacterial strains.
• Use precision CF mini-lung models to test the most promising medicines and combinations in a more realistic lung environment.

What could happen next?

The project has a potential pathway to clinical translation because the medicines under investigation have already been approved for other uses and have established safety profiles. This gives researchers a head start, as they can build on existing knowledge about these medicines rather than starting drug development from scratch. Their safety and effectiveness for treating NTM infections in people with CF will still need to be established.

If promising treatments are identified, the researchers will undertake further laboratory studies to confirm their effectiveness, test different doses and assess the best combinations. The most promising treatments could then progress towards early-phase clinical trials in people with CF.

The team will also work with clinicians and people with CF to help ensure the research addresses real-world treatment needs.

The goal is to move away from trial-and-error treatment and towards more targeted, effective therapies for people with CF living with NTM infections.