Biotechnology Focus August/September 2018

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R&D news Breathtaking therapy has high potential for spinal cord patients

Drs. Gillian Muir (left) and Valerie Verge. Photo: Debra Marshall New research from the University of Saskatchewan has scientists excited about the potential of a new therapy called acute intermittent hypoxia (AIH) for patients with partial spinal cord injuries. AIH therapy involves repeated exposure to low oxygen (hypoxic) levels for brief periods. This action triggers a chain of events in the nerve cells or neurons as they react to the mild stress. “The AIH alerts the cells that they’re under stress,” explains Valerie Verge, a professor of anatomy and cell biology in the College of Medicine. “The cell adapts by turning on specific genes and creating specific proteins that help the cell to survive the stress. They induce a strengthening of the existing neuronal connections which is referred to as plasticity.” As director of the Cameco MS Neuroscience Research Center, Verge has a keen interest in neurological research. She shares this passion with Dr. Gillian Muir, a professor at the Western College of Veterinary Medicine (WCVM) and the co-principal investigator in a recent study published in PLOS ONE. While Verge’s focus is on the cellular level, Muir is an expert in behavioural recovery after injury. She has collaborated on studies with professor Gordon Mitchell, a noted neuroscientist at the University of Florida, and she has been involved in multiple studies monitoring the functional recovery that occurs when AIH therapy is combined with rehabilitative training in patients with spinal cord injuries. The study used two groups of rat models with partial spinal cord injuries that received seven days of rehabilitative motor therapy, with only one group reviving the AIH therapy along with the daily regime. 6 BIOTECHNOLOGY FOCUS August/September 2018

Each AIH treatment consisted of 10 fiveminute cycles where the animals breathed hypoxic air (11 per cent oxygen) alternating with normal air (21 per cent oxygen). The research team compared the abilities of both groups each week as they performed specific motor tasks that had been mastered before the injury, and then they compared the cells in the spinal cords of both groups of animals. Results confirmed that AIH leads to increases in the amount of specific proteins within cells linked to hypoxia and plasticity. They also observed notable improvement in the functional abilities of the group that received both AIH and rehabilitative therapy. A noteworthy finding of the current study was evidence that the proteins connected with plasticity were increased in areas of the spinal cord other than just the injury site— an indication that hypoxia triggers a reaction from neurons in other parts of the body, including the brain. Since AIH treatments expose the whole body to hypoxia, it’s possible that the nerve cells of the peripheral nervous system and the brain are also reacting to the low-level stress by creating the proteins associated with plasticity. Verge and Muir are optimistic that AIH therapy will have a positive impact on a large spectrum of injuries and conditions that affect the nervous system; and although it is still too early to say, this study prompts further questions to the possibilities of AIH therapies and whether it can enhance the nervous system or even repair damaged cells. To see this story online visit https://biotechnologyfocus.ca/breathtaking-therapy-has-high-potential-forspinal-cord-patients/

Researchers discover a way to genetically screen for acute myeloid leukemia An international team of scientists discovers a technique that predicts healthy individuals who are at risk of developing acute myeloid leukemia (AML), which is an aggressive and often deadly form of blood cancer. The findings, published in Nature, illuminate the ‘black box of leukemia’ and answer the question of where, when and how the disease begins, says co-principal investigator Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre, University Health Network. “We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to AML. We can find these traces up to 10 years before AML actually develops,” says Dr. Dick. “This long-time window gives us the first opportunity to think about how to prevent AML.” Study author Dr. Sagi Abelson, a post-doctoral fellow in the Dick lab, says: “AML is a devastating disease diagnosed too late, with a 90 per cent mortality rate after the age of 65. Our findings show it is possible to identify individuals in the general population who are at high risk of developing AML through a genetic test on a blood sample. The ultimate goal is to identify these individuals and study how we can target the mutated blood cells long before the disease actually begins.” The study stems from Dr. Dick’s 2014 discovery that a pre-leukemic stem cell could be found hiding amongst all the leukemia cells that are present in the blood sample taken when a person is first diagnosed with AML. The team extracted the data from more than 100 participants who developed AML six to 10 years after joining the study, plus the data from an agematched cohort of more than 400 who did not develop the disease. The gene sequencing tool was a Continued on page 7


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