Alberta Innovates- Health Solutions

"I'm working at the opposite end of things from the rest of the lipid researchers," says Heritage researcher Dr. Gary Lopaschuk. "They're trying to find how lipids can be involved in causing heart diseases. I'm trying to find out what happens in cells when heart disease occurs."

A glance at his faculty appointments and research interests confirms that Dr. Lopaschuk likes to approach research from as many angles as possible. His official appointment to Pediatrics at the University of Alberta is complemented by his involvement in lipid research, and the cardiovascular research group. And, as if research weren't enough, he is entering the business world with the formation of a company, Metabolic Modulators Research Limited, to refine special technologies that measure metabolism (energy use) and to develop potential heart drugs.

For more than a decade, Dr. Lopaschuk has been studying how essential fats in cells are used as fuel by hardworking heart muscle. Stored in cells as fuel reserves, fat metabolism in the body increases in specific situations-trauma, fright, starvation-that require high energy. Heart muscle with its ceaseless contractions also requires high energy, but it has to use fats along with stored sugar (which is broken down to form glucose), in a healthy balance.

This delicate sugar/fat balance is thrown out of kilter when heart tissue experiences trauma. After a heart attack or during a heart operation, when the heart is stopped and then started again, a flood of fatty acids is released into energy-depleted heart cells in a process known as fatty acid oxidation. Fat needs more oxygen to be used by cells than glucose, putting even more strain on vulnerable heart tissue and often resulting in permanent damage from oxygen starvation. The sooner doctors can reintroduce oxygen and get the heart working again, the less likelihood there is of heart damage.

Dr. Lopaschuk began investigating ways that traumatized heart cells would use less damaging levels of fat. In a wonderful example of how different paths in research can intertwine and result in unexpected knowledge, his investigations led him to test two drugs developed years ago to help diabetics use sugar better. The drugs had remarkable results. When treated, traumatized heart cells are stimulated to use glucose instead of fat, a way of getting fuel that requires less oxygen and prevents damage.

The patents on these drugs, however, will expire in a short time, after which they will become public domain. There will be less incentive for pharmaceutical companies to spend millions developing them as heart drugs because profits would be less assured.

Dr. Lopaschuk has zeroed in on the key enzymes where these drugs work as heart medications. With the collaboration of Dr. John Vederas, a University of Alberta chemist, he is modifying the drugs and selecting the ones that are most important. Since the new compounds would differ from the original drugs, they can be patented.

The new patents may open the doors for pharmaceutical investment and development. Commercialization is not without its risks. The prevalence of heart disease and its position as the number one killer in North America means that the race to get to market with new drugs is intense and the stakes very high. Dr. Lopaschuk figures he has one to three years to develop the new compounds.

The new technology he has developed to measure the amounts of fat versus sugar used by heart cells has enabled the identification of key enzymes in heart muscle that control fat use. He is hoping to develop compounds that work on these enzymes as well.

Dr. Lopaschuk has collaborated with Heritage researcher and pediatric cardiovascular surgeon, Dr. Ivan Reybeka and a pediatric cardiologist, Dr. Ruth Collins-Nakai to test some of the new compounds on desperately sick newborns. The results have been very promising.

Dr. Gary Lopaschuk is a Heritage Senior Scholar. He has received support from AHFMR's Technology Commercialization Program to help commercialize Metabolic Modulators Research Limited technologies and products. He also receives support from the MRC, the Heart and Stroke Foundation of Alberta and the Northwest Territories, and the Canadian Diabetic Association.