Phage Therapy

Phages, or bacteriophages, are the natural enemy of viruses. They are the most abundant organisms in the biosphere.

Researchers have used phages as treatments before, however after the 20th century, the practice mostly disappeared.

But, just recently, an engineered phage therapy has proven to be a successful treatment for a Cystic Fibrosis patient.

A Cystic Fibrosis Story

A 15-year-old living with Cystic Fibrosis (CF) in London was in desperate need of a new therapeutic option. After a double-lung transplant (which itself was successful), the teen faced a severe reaction to the IV drugs given to her in an effort to keep her infection-free. She faced diarrhea, nausea, and anorexia, ultimately forcing doctors to stop the therapy. But, within a week off of the infection fighting drugs, infection sparked. The bacteria was Mycobacterium abscessus, which is similar to tuberculosis. It was multiplying in her skin, fluids, and organs. Antibiotics weren’t proving effective at treating the bacteria, and instead were causing liver damage.

Nine months after her surgery, she couldn’t eat, could barely talk, and her doctors lost all hope. She was sent home with palliative care so that she could at least see her friends before she died.

But the girl’s mother was determined to fight. She asked the doctors about phage therapy. Unfortunately, her doctor Helen Spencer didn’t know much about the treatment. But, a microbiologist in the same hospital named Dr. James Soothill had experience in the area and stepped in to help.

Soothill sent an email to Graham Hatfull, who he’d met back in the 1990s. Hatfull runs a lab at the University of Pittsburgh which is an international repository for phages. Students worldwide working to identify new phages (of which there are trillions) send their findings to Hatfull’s lab. The lab now houses over 10,000 viruses.

After hearing this CF patient’s story, Hatfull began looking for a phage that could combat the bacteria. It wasn’t an easy task as each phage only infects specific strains of specific bacteria. To make matters more difficult, most of the samples in Hatfull’s lab came from a different species of bacteria than what the patient had. So, in addition to sifting through the samples he already had, he also asked his students collect more samples to investigate.

Only one sample proved effective, and it was one they already had stored. It was named Muddy by Lilli Holst, the undergraduate who discovered it at the University of KwaZulu-Natal in South Africa. She found it on a rotten eggplant back in 2010.

An Engineered Phage

While it was amazing that Muddy was effective, the researchers knew they needed to find at least two more effective phages. If they gave the patient just a single phage, it would be likely that the bacteria would build a resistance to it very quickly.

The team had found other phages that were active against the bacteria, they just weren’t as effective as Muddy was. So, they engineered the phages, deleting the DNA that suppressed their instinct to kill the bacteria. Since they hadn’t added anything to the viruses, they were easily passed through regulations and the team was able to send the two engineered phages and Muddy to the CF patient in London.

It was the very first documented engineered phage used in a human patient.

First, the treatment was administered only to her external wounds. Then, it was injected into the bloodstream. Slowly, she began to heal. The wound on her chest closed, her redness faded, her skin infections subsided, the bacteria disappeared from her phlegm and blood serum, and it subsided within her internal organs.

It’s now been almost a year since she was given the therapy, and while the bacteria isn’t completely gone, she is now eating, attending school, and even learning how to drive.

It’s truly miraculous.

However, some resistance has been documented in her fluid samples. So, Hatfull is working on finding new phages to add to her treatment cocktail.

The results from this CF story were published in Nature Medicine. 

The Future of Phage Therapy

There’s still a lot of research to do in terms of phage therapy. Unfortunately, this CF story doesn’t have the weight that a clinical trial would have. It doesn’t prove that all engineered phage therapies are safe or effective. However, this patient’s story is encouraging and continues to indicate the promise phage therapy has as a treatment.

That said, many researchers still have reservations about the treatment. They aren’t sure whether or not it will be able to be scaled up to the level needed to combat the global crisis surrounding antibiotic resistance. Unfortunately, each therapeutic developed for a single strain of a virus necessitates an exquisite amount of research. Some scientists are apprehensive about whether or not companies will be able to obtain the level of evidence needed to get their investigative therapies approved.

However, companies are still working hard to develop personalized and general, natural and engineered, phage cocktails. Clinical trials in humans should be coming in the near future.

You can read more about this Cystic Fibrosis story here.