Phage therapy: 'Viral cocktail saved my daughter's life'

Teenager recovers from near death in world-first GM virus treatment

Teenager recovers from near death in world-first GM virus treatment

This old-time approach to battling bacterial infections might be worth another look in these days of antibiotic-resistant bacteria, a new paper argues.

She had undergone the procedure in a similar time frame to another teenager who was also suffering from massive infections that were spreading across their skin and through their tissues. Isabelle, for example, had lost two-thirds of her lung function.

Physicians turned to the experimental treatment to save 17-year-old Isabelle Carnell-Holdaway, a cystic fibrosis patient in England who contracted a life-threatening infection after a lung transplant in 2017.

Researchers detailed this process in an article published May 8 in Nature Medicine.

Genetically engineered phages - viruses that kill bacteria - have been used for the first time to treat a patient struggling with a risky, persistent superbug infection.

Within a week, the surgical wound became red with infection.

When she started immunosuppressant drugs to prevent her rejecting the transplant, the infection came back.

Spencer described her prognosis at this point as "very poor". The patient had died earlier that month.

"The idea is to use [phages] as antibiotics - as something we could use to kill bacteria that cause infection", Hatfull said.

Isabelle's mother Jo, of Faversham, Kent, learned of the treatment online - and the medics treating her at Great Ormond Street Hospital contacted leading United States researcher Professor Graham Hatfull. "We were totally devastated by that".

A teenager given a one per cent chance of surviving a unsafe infection has been saved by an experimental cocktail of viruses.

Doctors then infused her with 1 billion phages twice a day in June 2018, and applied the phage cocktail onto her skin lesions. And identifying the exact phage suited to tackle a specific bacterial infection can be a treasure hunt, as there are countless viruses and bacteria in the world.

Also known as bacteriophages, phages are a naturally occurring virus that attacks bacteria rather than the body's own cells.

"Cocktails of phages were used therapeutically in Europe and the United States during the pre-antibiotic era, and they are still prevalent in Russian Federation and Central and Eastern Europe today, for wound infections, gastroenteritis, sepsis and other ailments", wrote Charles Schmidt, a science writer, in a related article published in the journal Nature Biotechnology. But following the operation a drug- resistant "superbug" took hold.

Luckily, Spencer said, "one of our microbiologist consultants here did his thesis on phage therapy 20 years ago".

Isabelle's story is remarkable, but also only a single case.

Steffanie Strathdee, PhD, co-director of the Center for Innovative Phage Applications and Therapeutics (IPATH) at the UC San Diego School of Medicine, says the case is exciting on a number of levels.

Prof. Hatfull's main interests are the study of phages and the treatment of (TB), which is a bacterial infection that mainly settles in the lungs.

"This is the first use of "phages" to treat this kind of infection with this kind of bacterium, and it's the first time that anyone's used "phages" that have been genetically engineered to be more effective", said study co-author Graham Hatfull. "Despite the fact that phage have been a subject of research for almost a century, very little is known about them", he wrote. Hatfull and team then came up with was to modify the genomes of the two less effective phages to render them fully effective against the bacteria they needed to attack.

Her parents chose to take her home where she would be surrounded by family.

"We're just so grateful and just so thankful and so relieved and just so happy that we've still got her with us", says Isabelle's mother, Joanne. "She just could not walk".

But Hatfull warns that phages are not a mass cure for resistant infections.

She was incredibly sick. "Her appetite improved. She's had weight gain". "She's just loving her life".

Spencer is also hopeful, if more guarded: "We are dealing with microbacterium, and in treating it, we know this is a long game; it's not a short fix".

"We haven't cured her", Spencer said, adding that that today, 11 months since the start of Isabelle's treatment, the bacterium is still causing skin lesions "on occasion".

Isabelle's mother Jo urged doctors at Great Ormund Street to contact Graham Hatfull, a professor of biological sciences at the University of Pittsburgh in the U.S., who specialises in phage research.

But as with all such case reports, the impressive details of how this work was accomplished - on top of the eggplant scraping, it involved a chance encounter in the Republic of Georgia, a close examination of some bird guano, and a loophole in British regulation of genetically modified organisms - make clinicians wonder to what extent the development can be scaled up to help combat the global crisis of antibiotic resistance. To begin with, the team found three potentially useful bacteriophages. Still, production costs "pose a major hurdle", and much remains unknown about phage biology.

However, scholars explain that the initial enthusiasm regarding the potential of phage therapy for many years.

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