July 1, 1999 Toronto -- Researchers at The Hospital for Sick Children (HSC) and the University of Toronto (U of T) have used a toxin produced by the same bacteria that cause hamburger disease to completely eliminate malignant human brain tumors grown in mice. The research is published in the June issue of the scientific journal Oncology Research.
"E. coli is a common gastrointestinal bacterium," explains Dr. Cliff Lingwood, a senior scientist at HSC and a Professor of Laboratory Medicine and Pathobiology at the U of T. "Some E. coli strains produce a toxin known as verotoxin. Our earlier research has shown that, in the test tube, verotoxin kills certain brain tumor cells very efficiently. We wanted to determine if this was also the case in a living animal."
As part of her doctoral studies in Dr. Lingwood's laboratory, Dr. Sara Arab (now a clinical fellow in Medical Genetics at HSC) injected verotoxin directly into human astrocytoma brain tumors that had been grown in mice. After a single injection, the tumors had shrunk by half within 48 hours. Within seven to 15 days the tumors had completely disappeared and had not reappeared by the end of the experiment (60 days). Both the tumors and their blood vessels were killed by the toxin.
"We are very excited by this observation because astrocytoma is the most common type of malignant brain tumor and the prognosis is poor for patients with this diagnosis," explains HSC neurosurgeon James Rutka, a collaborator in the research and head of the Arthur and Sonia Labatt Brain tumor Research Centre. Approximately 20,000 people are diagnosed with brain tumors each year in Canada and the United States. "This discovery could be very promising because the verotoxin makes a two-pronged attack on the tumor: it destroys tumor cells and shuts down the tumor's blood supply."
While earlier HSC research has demonstrated that verotoxin-producing E. coli can cause kidney failure, primarily in very young children, the scientists suggest that a window of opportunity exists for verotoxin treatment in older patients.
### Plans are already underway for the next phase of the research: preliminary clinical trials in older children and adults. In that trial, verotoxin will be injected into residual glioblastoma cells following surgical removal of the majority of the tumor. Glioblastoma is the most malignant form of astrocytoma.
This research was supported by the Medical Research Council of Canada and The Hospital for Sick Children Foundation. Select Therapeutics Inc. holds an exclusive licensing agreement with The Hospital for Sick Children to bring the benefits of this research to market.
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