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Canadian Study Using Phages Offers Hope for Huntington's Disease Patients With Superbug Infections

"It's a life-changing breakthrough. Finally, there's hope," exclaimed Victoria Marshall, wiping away tears as she read a text message from her doctor containing the latest test results.

For individuals living with Huntington's disease (HD), frequent visits to hospitals worldwide expose them to the risk of contracting superbugs like MRSA and C. diff. These infections pose a significant threat to their already compromised immune systems. However, a groundbreaking Canadian study employing phages to treat superbug infections is now underway, offering a glimmer of hope for those affected.

Victoria Marshall, a 72-year-old retired librarian, has been battling urinary tract infections (UTIs) since the age of 65. UTIs are prevalent among individuals with HD, affecting approximately one in four women over their lifetime. Marshall endured excruciating pain and a constant burning sensation, which confined her to the closest bathroom.

"I experienced sharp, burning pain almost all the time, a sense of urgency, and occasional dampness," Marshall shared with CTV News. "I couldn't leave the house for more than an hour without knowing where the nearest bathroom was."

Unfortunately, none of the half-a-dozen antibiotics prescribed to Marshall could eliminate her treatment-resistant E. coli infection, also known as a superbug infection. Even intravenous administration of powerful drugs failed to eradicate the bacteria and led to debilitating side effects such as nausea and body pain.

As the infection advanced up her urinary tract, Marshall faced the removal of one of her kidneys, with the fear of the other being at risk as well. She reached a point of desperation, realizing that the available options were exhausted. "By the end, it was like we had run out of options. There was nothing else. It's scary," she expressed.

In May, Marshall became the first patient in a Canadian study led by Dr. Greg German, an infectious disease physician at St. Joseph's Hospital in Toronto, which utilizes phages to treat treatment-resistant UTIs. Driven by his fascination with phages as a potential tool against the escalating threat of antibiotic-resistant infections, Dr. German embarked on this groundbreaking endeavor.

"Phages shoot to kill, and they have a natural ability to target the source, replicate themselves, and persist as long as the infection persists," explained Dr. German.

Phages, present wherever bacteria are found—in water, soil, and sewage—function like viral smart bombs. They selectively attack bacteria, injecting their DNA to produce more phages until the bacteria explode, releasing billions more phages that seek out new targets.

In the clinical trial, three strains of phages were carefully chosen to specifically target Marshall's strain of E. coli infection. These phages were collected and purified in a lab at Baylor College of Medicine in Houston, Texas, where researchers are also investigating the use of phages for UTIs.

Dr. German emphasized the personalized nature of this treatment, stating, "They all target E. coli, drug-resistant E. coli that we couldn't eliminate by any other means. Daily IV antibiotics are not a long-term solution."

Although phage therapy is not yet available in Canada, it was a French Canadian scientist, Felix d'Herelle, who co-discovered this treatment approach in 1917. Marshall's bladder was infused with billions of phages, while some were applied topically to her vaginal area, and she even consumed some orally to ensure their delivery into her urinary tract. Compared to weeks of antibiotic therapy, Marshall refers to phages as her "one-shot treatment."

"Within about 48 hours, I started feeling better," shared Marshall.

When bacteria levels began to rise shortly after the treatment, doctors administered a mild antibiotic that had previously been ineffective. It is suspected that the presence of phages may render treatment-resistant bacteria more susceptible to standard antibiotics.

"I feel like a new person," Marshall exclaimed, as confirmed tests showed her to be infection-free even a month after the phage therapy. Prior to receiving this treatment, her infection would have typically recurred within days, according to Dr. German.

"We are thrilled with the progress we have seen so far. We eagerly await the data from our collaborators to demonstrate that the infection is truly eradicated," he stated, acknowledging that the research is still in its early stages. Dr. German recently presented Marshall's case at a gathering of phage scientists during the Viruses of Microbes meeting in Tbilisi, Georgia.

Steffanie Strathdee, the head of the Centre for Innovative Phage Applications and Therapeutics (IPATH) at the University of California in San Diego, expressed her excitement regarding the advancements in phage therapy in Canada. Strathdee, a Canadian scientist herself, successfully utilized phages to save her husband, Tom Patterson, from a nearly fatal superbug infection, as chronicled in her book "The Perfect Predator" and featured in a CTV W5 documentary.

IPATH not only facilitates connections between patients suffering from treatment-resistant infections and phage scientists but has also treated numerous individuals globally. They have been consulted on cases involving respiratory infections, as well as infections stemming from hip or knee replacements that are challenging to treat.

Dr. German has been receiving inquiries from Canadians afflicted with superbug infections who are eager to explore phage therapy. While compassionate use of phages is permitted in the United States and parts of Europe, Canadian regulators require formal clinical trials to assess safety. Dr. German believes his phase one study holds significant importance, as it will involve testing phage therapy on an additional 200 women with treatment-resistant UTIs in Ontario. The results obtained from these trials will contribute to establishing the safety profile of phage therapy for Health Canada, with expectations of completing the evaluation within two years.

"Based on our global experience with phage therapy, everything indicates that it is safe and ready to progress to the next stage," Strathdee affirmed.

As Marshall continues to document her symptoms and potential side effects in a diary, she remains a staunch advocate not only for phages but also for women enduring similar struggles without viable solutions. She encourages others not to fear this innovative treatment, noting its ease of administration and minimal side effects.

Phage therapy, initially discovered by a French Canadian scientist, Felix d'Herelle, over a century ago, began in Canada. Early studies showcased the effectiveness of phages in controlling outbreaks of dysentery and typhoid fever. However, antibiotics gained prominence due to their mass-production capabilities and profitability, relegating phages to the periphery of mainstream medicine. With the rise of antibiotic-resistant superbugs, bacteria have evolved, resulting in an increasing number of treatment-resistant infections among patients with joint replacements, organ transplants, and undergoing cancer therapy.

A recent report projects that nearly 400,000 Canadians could lose their lives to superbugs within the next three decades. The World Health Organization has also cautioned about entering a post-antibiotic era, wherein even a simple skin infection can prove fatal.

It is essential to note that while men can also contract UTIs, these infections are more prevalent among women and individuals with vaginas, partly due to the shorter length of their urethra, facilitating easier entry of bacteria into the urinary tract.



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