Ottawa doctor helping to bring back old treatment for new problems

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An Ottawa doctor’s race to find a last-chance treatment for a patient fighting an artificial joint infection could help spark a Canadian resurgence of an old therapy to treat new medical issues.

That treatment is phage therapy. It uses viruses that target bacteria, called phages, to fight bacterial infections. Phage therapy is commonly used in some parts of the world but it is experimental and only available through clinical trials in Canada.

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It is attracting new attention at a time when antibiotic resistance is a growing concern. Some of that attention is now focused on Ottawa.

Earlier this year, a 79-year-old Ottawa-area resident became the first in Canada to receive groundbreaking phage therapy to treat a periprosthetic joint infection (involving an artificial joint) after all standard treatments failed.

Dr. Marisa Azad, the infectious disease physician and associate scientist at the Ottawa Hospital who administered the phage therapy at The Ottawa Hospital last spring, knew her patient’s life was on the line.

That patient, Thea Turcotte, had been an active senior until she slipped on ice and shattered her hip and pelvis, requiring a double hip replacement.

By the time Azad saw Turcotte at her clinic at the Ottawa Hospital, the patient had undergone more than a dozen surgeries and numerous antibiotic treatments in an attempt to treat recurrent infections, without success.

Such infections are rare, but difficult to treat. Treatment can involve cutting out the infected areas, removing the implants and treating with antibiotics, but often biofilms cover the artificial joints and surrounding tissue, which make treatment more difficult, said Azad. Those treatments had not stopped Turcotte’s infection. To complicate matters, Turcotte was severely allergic to several major classes of antibiotics, which limited options further and she could not withstand any more surgery, said Azad.

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“She would not survive. There were no good surgical options and no good antibiotic options,” said Azad.

“That is when I thought about phage therapy.”

Azad says she had long been interested in phage therapy. She had read about its history and learned about its growing use in some parts of the world.

Azad got in touch with the Winnipeg-based company Cytophage Technologies Inc. They collaborated with her on treatment for the patient. Health Canada approved its one-time use after Azad warned the patient would likely die without the experimental treatment. It worked.

Now, six months later, Turcotte’s wound has healed and her mobility is improving.

“This marks a momentous time point given that we have now met the definition of clinical ‘cure’ or control of infection,” said Azad.

The treatment and protocol developed by Cytophage Technologies Inc. and Azad’s research team to successfully treat the artificial joint infection is the subject of a soon-to-be published study. Its authors expect it to be a springboard for a larger trial on phage therapy in Canada and even the development of the country’s first phage centre of excellence.

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The use of phage therapy is gaining attention as an alternative to antibiotics during a period of growing antimicrobial resistance. In addition to the experimental treatment in Ottawa last year, the technology also been used experimentally to treat chronic urinary tract infections.

Phage therapy has been around for almost a century. French-Canadian microbiologist Felix d’Herelle, known as the father of phage therapy, discovered bacteriophages in 1917. The treatment fell out of favour in much of the world with the advent of antibiotics, but it continued to be used in the Soviet Union and later Russia where phage preparations are registered medicines and there are dedicated research centres. It is also beginning to be more common in other parts of the world, including some European countries.

There is a growing buzz around their project said Azad. She and other researchers are receiving inquiries from patients and researchers around the world “which is very exciting”.

Phages, also known as bacteriophages, are viruses that solely kill and selectively target bacteria cells, by attaching to them. They do not affect human or animal cells. Steven Theriault, chief executive officer and chief scientific officer of Cytophage Technologies compares phages to a “lunar lander”. Those “lunar landers” push genetic information into the bacteria, enabling the phage to replicate itself hundreds of time. They are able to kill multiple types of bacteria.

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Theriault, who previously worked at Canada’s National Microbiology Laboratory, said he became interested in the possibilities of phages and worked on the project on weekends before leaving his job at the lab to pursue phage development full time.

“Phages fascinated me. I fell in love with trying to develop a platform for a phage able to kill multiple types of bacteria,” he said.

When Azad contacted Cytophage for help with treatment for Turcotte, the company checked their library of phages against bacteria samples and found “some hits” – meaning phages that could kill the bacteria.

Cytophage became the first Canadian company to treat a prosthetic joint infection in Canada, something that the company and Azad, in collaboration, hope to repeat with more one-off treatments. Azad is currently leading a multi-centre Phase 1 clinical trial with Cytophage in Canada and, potentially, the U.S. to study the use of phage therapy on patients with artificial joint infections.

Theriault said there are numerous possibilities for the use of phage therapy – in humans and in animals. His company’s products are currently being used as alternatives to antibiotics in some livestock, including a project involving swine in Manitoba.

“Bacteriophage gives physicians another strategy that they can use for treatment,” Theriault said.

His company takes natural phages and genetically modifies them for specific uses.

“That what is the fascinating thing about bacteriophage research,” said Theriault. “it is basically an open door to create solutions to problems by using what Mother Nature already gave us.”

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