Health Care

Genetically Modified Viruses Save Teen From Superbug

Genetically Modified Viruses Save Teen From Superbug”

The life of a teenager suffering from a deadly infection has been saved thanks to a revolutionary treatment using a cocktail of viruses.

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

Now Isabelle is still receiving the treatment, but has returned to school, and is learning to drive.

"The specificity is definitely our friend in terms of using phages in antimicrobial treatment", Hatfull said.

Phages work by infecting bacteria cells and killing them, but they are very specific in which infections they can target.

They inject their genetic code into risky bugs, forcing them to produce more phages.

Within a few months, they found the set of phages that could match the bacteria infecting one of the patients. "They're very specific, it's a targeted strike, you're not going to affect the rest of the microbiome and they're low toxicity because they don't infect human cells".

Isabelle Carnell-Holdaway, 17, began the experimental treatment after doctors lost all hope. She had cystic fibrosis, a genetic disease that clogs lungs with mucus and plagues patients with persistent infections. "Our expertise is in the study of the bacteriophages, so we sought to try to find phages in our collection which would infect and kill this particular bacterial strain".

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

"I know that because of the experience that I've had with other patients who have had a transplant and who were infected with MB", Spencer said. She was underweight, had liver failure, and lesions on her skin from the infection.

Doctors said there was nothing they could do, and that Isabelle had a less than 1% chance of survival. In a radical act to improve her quality of life, she had just undergone a double lung transplant, and all seemed well until massive infection started seeping out of her sutures.

The team at Great Ormond Street contacted Prof Graham Hatfull, at the Howard Hughes Medical Institute, in the USA, who had the world's largest collection of phages.

"It's probably going to turn out that the phages are going to be really effective for some conditions, and others they won't work that well", he said.

The US team settled on three phages - two of which they genetically modified to make them more effective.

When it came to identifying the phages that may be able to help the 15-year-old patient, the search was not so smooth. The therapy was injected into her blood stream twice daily and applied to the lesions on her skin, according to Nature Medicine.

"Over 8 weeks, 20 additional skin nodules appeared on arms, legs, and buttocks, and the surgical wound showed areas of breakdown", the study said. Around the same time, Jo had been told her daughter was unlikely to survive. She named it Muddy and got on with her life, earning more degrees, landing a job at a communications agency. She passed her GCSE in maths, is studying A-levels and enjoys baking and gardening.

She is still having two infusions of the viral cocktail every day. With the new treatment, she has not been completely cured.

Image caption This vial contains the mix of phages that are treating Isabelle's infection.

She added: 'It's wonderful really, but also tinged with sadness when I think of all the patients that did not survive as the treatment was not available in time for them'.

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

Dr Spencer added: "We have to be really cautious about extrapolating a single individual case to other patients and what it might mean for them".

Now, researchers at the University of Pittsburgh in Pennsylvania and the Howard Hughes Medical Institute (HHMI) in Chevy Chase, MD, provide evidence that a different approach can offer an effective way of fighting off unsafe bacterial infections.

The idea of using bacteriophages to battle human disease has been around for about a century.

The field developed in Georgia and other countries in the former USSR, but never became mainstream medicine.

The new study is supported by several previous research papers which have explored the potential of phage therapy.

One antibiotic can work across a broad range of bacterial infections, while phage-therapy requires finding the precise phages that will attack each infection. Could they hold the answer to antibiotic resistance?

Spencer said: "The bigger question is whether it could be used to treat other resistant bacteria".

Hatfull and his team spent 3 months searching for phages that could kill M. abscessus isolated from Isabelle's wounds and sputum.

"The antibiotic pipeline is rapidly running dry and the use of bacteriophages is increasingly proving to be one important solution to the looming infectious disease crisis the world faces", he added. If a phage could do that, the team reasoned, it might able to fight the patients' infections. The antibiotic-resistant bacteria infected her liver, lungs and surgical wound.

Follow James on Twitter.



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