Research Update 

Cure4CF is funding a cutting-edge study in personalised bacteriophage treatment in CF, so what’s it all about?

What are bacteriophages?

Bacteriophages or phages for short, are viruses that specifically target and kill bacteria.  These viruses are the most abundant organisms on earth. It is estimated that there are more than 10³¹ phage particles across the land, air and water.  Given that one trillion is 10^12, that is a lot of phage power out there! If you want to know more, check out this video on YouTube.

History of phages in medicine

The earliest reports of phages being used in medicine are from around 1915, they were even produced in the 1930s by some companies in the USA.  Early promise in phage therapy highlighted the need to understand the biology behind how phages work and kill bacteria.  More research was warranted. Around the same time penicillin was discovered and the desire to investigate phages as an antibacterial therapy rapidly decreased.  You can read more about the history of bacteriophages here. We now understand more about phages, what they are and how they work. Science is in a better place to use their unique capabilities to reduce harm caused by their natural targets – bacteria – and targeting infection-causing bacteria shows promise to reduce disease.

Why phage therapy is needed to target Pseudomonas aeruginosa

Pseudomonas aeruginosa is one of the most common causes of infections. These infections are often associated with health care settings and found in people with chronic lung diseases, particularly cystic fibrosis.  Some types of Pseudomonas are resistant to nearly all antibiotics and the world health organisation has categorised this type of Pseudomonas as CRITICAL in terms of a priority for new treatments.

The superpower of bacteria is to adapt to their environment, and avoid being killed by our bodies and by antibiotics. While scientists study bacteria in their laboratories, once in our bodies, bacteria can behave very differently.  They can form a biofilm (see image below), which is a large aggregate or clump of bacteria which are much less susceptible to antibiotics. Bacteria like Pseudomonas that form biofilms are particularly hard to treat.

In the 2021 report, the Australian CF Data registry reported that 69% of all samples tested were positive for Pseudomonas aeruginosa.  It was more common in older people but even those younger than 7 years old also had samples where Pseudomonas was isolated.

While the introduction of modulator therapy has been game changing for many people with CF, there is little evidence that these therapies impact on chronic lung infections.   This means people are still reliant on antibiotics to remove infection.

What we know about Pseudomonas aeruginosa in young people with CF

1 in 4 children with CF are estimated to be infected by Pseudomonas aeruginosa.

Having Pseudomonas aeruginosa puts children at 2.8x more at risk of dying within 8 years.

Children with Pseudomonas aeruginosa have more hospitalisations.

Cure4CF Phage study

Dr Jagdev Singh and his team have recently published their clinical trial protocol in BMJ Open Respiratory Research, you can see the full manuscript here.  This is one of two important research studies funded by Cure4CF in 2023.

How will the study work?

1. Eligible children will provide a sputum sample and the bacterial strain of Pseudomonas will be identified.
2. The specific strain of bacteria isolated from the person will be tested against the library of phages that are available for Pseudomonas. This is like finding the right key for a lock.
3. The phage is then prepared in the laboratory and extensively tested for purity and safety. The team will also check the phage and how it responds to the medicines the child with CF might be taking.
4. The phage vial is then tested once more before being administered to the person. Initially using bronchoscopy on day one and then by nebuliser daily for a further 6 days.
5. The child will be carefully monitored to see how they feel and how their infection responds to the treatment.

Read more about Cure4CF funded Clinical Trial on our webpage.