Kermode on cutting edge of genetics

May 01, 2003, vol. 27, no. 1
By Carol Thorbes

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A special look at health research

As one of Canada's top-ranked comprehensive universities, SFU has no medical school. Yet 130 faculty and their students, representing departments ranging from gerontology to molecular biology and biochemistry, are involved in ground-breaking medical and health-related research. “We want to depart from the conventional clinical models of health research and education,”says President Michael Stevenson. “By drawing on our interdisciplinary strengths, there are very real opportunities in areas such as health promotion and population health to explore.” These stories showcase SFU's prowess in the medical and health research field.

Allison Kermode (centre), associate professor of plant cell and molecular biology at SFU, looks at transgenic plants produced in her lab. SFU research assistant Sabine Clemens (right) and Shauna Lauzon, a fourth year student in cell biology and genetics at UBC, are on her research team.

Imagine fields of tobacco, canola or maize destined to become transgenic (genetically transformed) hosts for the production of human enzymes or proteins that are ultimately used to treat diseases.

Sound farfetched?

Not when you consider the cutting edge research of Allison Kermode, an associate professor of plant cell and molecular biology at Simon Fraser University, and Lorne Clarke, an associate professor of medical genetics at the University of B.C. They are trying to use genetically modified plants to produce a human enzyme in an effort to treat a devastating childhood disease.

After two years of research, they have now successfully introduced a human gene into several plant species for the production of a lysosomal enzyme that is missing in children suffering from a progressive, hereditary metabolic disorder called MPS I. The disorder affects one in 100,000 in Canada.

Without the missing enzyme, the children's bodies are unable to break down certain molecules, such as complex sugars, a process required for the body to maintain healthy tissues. The result is a host of multi-system problems, including mental retardation and skeletal deformity. Severely afflicted children can die before age 10.

Kermode's research team is using many innovative strategies to engineer plants that can produce the human lysosomal enzyme needed to treat MPS I.

“Kermode's internationally recognized work in understanding plant protein targeting makes us a strong team,” says Clarke, a pediatrician at British Columbia's Children's hospital who diagnoses children with MPS I and follows the affected families.

The duo faces many challenges in getting a transgenic plant to host the production of human lysosomal enzymes. Kermode notes, though, that plants, particularly seeds, have several advantages over mammalian cell cultures for producing proteins of pharmaceutical interest.

“Plants can be genetically transformed with relative ease and seeds naturally store proteins in high quantities,” explains Kermode. “Transgenic plants do not need to be field-grown and the transgenic seed can be stored in the dry state, providing a stable source of pharmaceutical proteins.”

Once produced in sufficient quantities, the plant-produced human lysosomal enzyme will be tested on a mouse model of MPS I, which was developed by Clarke's group. Clinical trials in MPS I patients would then follow.

“Because the cells of our body generally have the ability to scavenge lysosomal enzymes introduced intravenously, enzyme replacement therapy is one way of supplying adequate amounts of active enzyme to patients,” says Kermode.

Transgenic plants could greatly lower production costs in comparison to mammalian-based systems for synthesis of human lysosomal enzymes. “The current estimated cost of this therapy, using animal cells, is approximately $200,000 to $300,000 annually per patient,” says Clarke.

The duo's research has attracted almost $1 million in federal funding from the Natural Sciences and Engineering Research Council and a pharmaceutical company is contributing its expertise.

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