Canadian Researchers Discover Gene Responsible for Regulation of HDL Cholesterol Levels

Vancouver, August 3, 1999 - Canadian researchers announced today the discovery of a gene responsible for two genetic diseases that result in low levels of HDL or "good" cholesterol and a highly elevated risk of cardiovascular disease. The research, published today in the journal Nature Genetics, provides insight into how HDL cholesterol levels are regulated in the body and may lead to new treatments for cardiovascular disease. The discovery was a result of a pan-Canadian collaboration, involving Xenon Bioresearch Inc. and a consortium of Canadian and international research institutions.

"Although medical science has developed effective methods to lower LDL or 'bad' cholesterol, until now we have not understood crucial mechanisms which elevate levels of HDL cholesterol. Our research reported today explains an important genetic cause for HDL cholesterol deficiency and provides crucial insights into mechanisms for preventing cardiovascular disease," said Dr. Michael Hayden, principal investigator in the study. "By studying two diseases which had previously appeared to be separate in cause, we have located similar genetic mutations in the same gene which result in low HDL cholesterol and a significantly increased risk of cardiovascular disease. This genetic target may provide a method for developing compounds to elevate low HDL cholesterol levels, the most common abnormality associated with cardiovascular disease."

HDL cholesterol is necessary for transporting cholesterol out of cells. A reduced level of HDL cholesterol is known to be directly related to increased coronary artery disease. By analyzing the most common condition of Familial HDL Deficiency, a genetic disorder which causes early onset of heart and cardiovascular disease, as well as the more rare and severe Tangier Disease, the research team located mutations in the ABC1 gene which impair the body's ability to regulate levels of HDL cholesterol. Working with families from the Netherlands and Quebec who have a history of heart disease, the research team revealed that a faulty ABC1 gene is linked to defects in the transfer of cholesterol from the body tissues to HDL molecules which then transport cholesterol to the liver where it is excreted.

"Approximately half of all people with coronary artery disease have low levels of HDL cholesterol, yet despite the world-wide impact and prevalence of cardiovascular disease linked to this disorder, there is no effective drug treatment for elevating HDL cholesterol levels," said Frank Holler, President and Chief Executive Officer of Xenon Bioresearch Inc. "This discovery is a significant breakthrough in the understanding of one of the most common forms of cardiovascular disease and one which we expect to very quickly incorporate into our research program to develop treatments to elevate HDL levels. Xenon's role in this research is a demonstration of the technology platform we have developed for genetic discoveries and the strength of our genomics collaborations both in Canada and internationally."

The paper published today in Nature Genetics is entitled, "Mutations in the ABC1 transporter gene in Tangier Disease and Familial HDL Deficiency" and was authored by Xenon in partnership with the Centre for Molecular Medicine and Therapeutics in Vancouver; Children's and Women's Health Centre of British Columbia; the Clinical Research Institute of Montreal; the Canadian Genetic Diseases Network; the Universities of British Columbia, Victoria, Toronto, and McGill; the Academic Medical Centre in Amsterdam, the Netherlands; and the National Research Council of Canada. Funding for this research came from Xenon Bioresearch as well as through grants from the Medical Research Council of Canada, the Heart and Stroke Foundation of Canada, and the Networks of Centres of Excellence Program via the Canadian Genetic Diseases Network.

Xenon Bioresearch Inc. is a privately owned Canadian biotechnology company engaged in drug discovery using population genetics and functional genomics. Through its research into the genetic factors involved in common human diseases, Xenon is working to identify novel genes, metabolic pathways and drug targets in cardiovascular disease, diabetes and osteoporosis. These discoveries will be used for the development of new, more effective therapies for these diseases. The Company was established as a spin-off from the Canadian Genetic Diseases Network. Its operations have been fully funded to date through contract research agreements with pharmaceutical and biotechnology companies.