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Zebrafish lab at St. Michael’s helps identify new genetic disease and possible treatment

Toronto, May 27, 2016

By Leslie Shepherd

Dr. Xiao-Yan Wen his research co-ordinator Koroboshka Brand-Arzamendi in the Zebrafish lab
Dr. Xiao-Yan Wen his research co-ordinator Koroboshka Brand-Arzamendi in the Zebrafish lab.

The Zebrafish Centre for Advanced Drug Discover at St. Michael’s Hospital played a key role in a new study that identified a new genetic disease and helped explain why the brain and the skeleton need a specific sugar to develop properly.

Researchers in Canada and Europe looked at nine people ages 3 to 46, including some siblings, who had the same unusual combination of severe intellectual disabilities, lack of speech and poorly growing bones, to determine whether there was a single underlying cause.

In a study published in the prestigious journal Nature Genetics, they reported that all nine people had the same genetic mutation and thus the same disorder. All had an impaired synthesis of a sugar known as sialic acid, causing low levels of sialic acid in their plasma, urine and cerebro-spinal fluid.

From the Greek “sialon,” meaning saliva, where it was first found 60 years ago, sialic acid is a sugar derivative made up of 11 carbon atoms that helps cells to communicate with each other. It is found everywhere in the body, although the brain contains much more sialic acid than any other organ. [The sialic-rich brain is what distinguishes humans from the Great Apes]. Sialic acid is also known to help the development of babies. Human breast milk contains significantly more sialic acid than cow’s milk or infant formulas.

To confirm that the deficiency of sialic acid was the cause of this new disorder, Dr. Clara van Karnebeek, a pediatrician and biochemical geneticist at BC Children’s Hospital, and one of the study’s lead authors, turned to Dr. Xiao-Yan Wen, director of the zebrafish lab at St. Michael’s and a world leader in zebrafish research.

Zebrafish have become a popular organism for biomedical research. Zebrafish are vertebrates, they breed rapidly and prolifically and their hearts start beating at about 24 hours after fertilization. Because they are transparent, researchers can watch the effect of drugs injected into them in real time.

Dr. Wen was able to knock down the NANS gene that codes the enzyme responsible for forming sialic acid in the fish. Fish that had this genetic mutation had very poor skeletal growth. But when sialic acid was added to their water, the defect was successfully corrected.

Dr. Wen said this was the first time zebrafish had been used not just to confirm a disorder but to immediately test and confirm a possible treatment.

Swiss and Canadian researchers are exploring the possibility that sialic acid, given as a dietary supplement, could be a treatment for this newly identified genetic condition.

However, the significance of these findings goes beyond the disorder itself and may have an impact on human nutrition science.

“The observation that sialic acid is central to the development of brain functions may support existing suggestions to use sialic acid for the fortification of infant formula, to foster an optimal brain development, as well as that of nutritional supplements for elderly people to maintain their cognitive power,” said Dr. Andrea Superti-Furga, a professor in the Faculty of Biology and Medicine at the University of Lausanne, Switzerland, and another lead researcher in this study.

About St. Michael's Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.