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After the discovery of antibiotics, the western world focussed it’s attention on these “miracle drugs”, without appropriate consideration for the future challenges of resistance which we face today. Phages, viruses that infect bacteria whilst leaving human cells alone, are self replicating. This means that they build copies of themselves within the bacterial cell. This is problematic when it comes to clinical trials in the UK.
1: Clinical trials
To ensure maximum safety for the public, clinical trials rely on strict safety standards. Scientists refer to these standards as “good manufacturing practices” or “GMP”. One of which is the dose of a medicine used in the trial. However, if a medicine is able to make more of itself within the patient, scientists have little control over the number of phages in the patient’s body after the phages are given. As well as other barriers, legal and economic, phages remain limited to pre-clinical trials.
However, this does not mean that the UK has not seen successes relating to phage therapy. Under the use of “compassionate medicine” in the UK, a patient can receive an experimental treatment when all other options have been exhausted, and is likely to die without medical intervention. Whilst these cases are time critical, and infections in these patients are well established, there have been successes where phage therapy has brought patients out of the firm grip of superbugs.
Isabelle’s Story
Isabelle Carnell-Holdaway, a teenager at the time living in the UK, was taken into hospital with a severe infection. After all antibiotics failed, they turned to the use of compassionate medicine for help.
Living with cystic fibrosis meant that her lungs contained excessive levels of mucus, a breeding ground for harmful superbugs to hide. Such diseases can’t be cured with antibiotics. After a lung transplant, she required immunosuppressant drugs. These drugs are used to prevent a patient’s immune system from attacking the transplanted lungs, but at the same time, weaken the immune system from attack by superbugs. After becoming critically ill, Scientists set to work, and found 3 phages which were able to attack her infection (pictured above). The scientists then modified the DNA in these phages to make them even more effective against Isabelle’s infection. You can read the full paper here. Phage therapy brought her infection under control within weeks. The BBC reported on her case in 2019.
2: Lack of investment
There is a difficult cycle created when a medicine is stuck in pre-clinical trials. Researchers require investment to develop Phage medicine closer to GMP standards, yet investors want evidence that phage therapy works, in the form of clinical trials. So far, phages have only been used in highly complex, time critical and life-threatening diseases. Trials are essential to prove that phage therapy works in regular infections. This creates an uneven playing field when antibiotics are used in everyday infections, yet phage therapy is a last resort for the dangerously ill.
“the recent webinar series led by the World Health Organisation in collaboration with the Global AMR Research and Development hub, highlighted that phage therapy receives only ∼2% of public and philanthropic funding for AMR research, even though many projects target high-priority bacterial pathogens”
Find the full story here
Communicating complex scientific concepts to investors Is important. And has remained a significant barrier between scientists and investors in the development of new drugs. Investment in new antibiotics has fallen due to the high cost of development, and the rapid emergence of resistant superbugs that render these expensive drugs ineffective. Also, a patient only takes antibiotics for a few weeks, until the infection has cleared. Therefore, large pharmaceutical take the economically wise choice to invest in drugs that people need all the time such as insulin for diabetes, statins to control cholesterol, and so on.
I have written a short post on my LinkedIn about attracting investors, you can read it here
3. Manufacturing Phages
Whilst current research is promising, scientists need to continue to research into the potential risk of side effects, as is the case with any new drug. If you’ve read my article on “What is a phage”, you will already know that phages turn the bacterial cell into a phage factory. Whilst this is great for patients, it means that scientists have to make phages within a sample of bacteria taken from the patient. This means that as well as the phages, we also make harmful toxins, and debris produced by bursting bacterial cells. This all needs to be removed before we can administer a phage to a patient. However, scientists now have tools to make (and modify) phages without needing bacterial cells. These “cell free” systems are a key advancement in phage manufacturing.
If you’ve ever heard of Mr Potato head, a popular childhood toy from the movie “Toy Story” loved my many millennials, cell free systems can work in the same way. We can modify phage DNA to change the properties of the “legs” or “head” of the phage to make it more effective at locating harmful bacteria. switching out or combining the parts of many different phages to create more powerful ones to fight superbugs.
What does the future hold?
In my opinion, Phage Therapy is the most promising tool we have to fight antibiotic resistance. Not to replace antibiotics, but to work with them in combination. Through campaigns to UK parliament, investors and the public, we can raise awareness of this crucial tool and boost the UKs position in the landscape of phage research. Our colleagues around the world are making the most of the opportunities provided by phage therapy, social and economic. If we act now, the UK can secure its own place and benefit from the global community fighting against superbugs.