RPP Profile: Dr. Patrick Parfrey

Many Newfoundlanders have grown up with "the fear." For at least nine generations, mysterious sudden deaths have torn through Newfoundland families, killing men and women in the prime of their lives. Their hearts stopped without warning, and centuries of family stories include tales of grandfathers who slumped over at work, fathers who collapsed before bed, brothers who died on the back porch, and sisters who left them too soon. With so much death around them, members of these affected families not only worried for their own lives, but also harboured intense fear for the lives of their children.

After an exhaustive 12-year search, researchers from Memorial University in Newfoundland pinpointed the genetic culprit behind "the curse." Long before the gene was found, researchers knew that the disease causing these sudden deaths was Type 5 Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC5), a degenerative condition in which heart muscle is slowly replaced by fibrous scar tissue and fat as a result of damage. The disease usually leads to "disordered" electrical activity in the heart and often interferes with the heart's blood-pumping action. Unfortunately, for many of the people afflicted, the first symptom of ARVC5 is sudden cardiac death. In fact, the average life expectancy of men with ARVC5 is 41 years; the average for women is 71.

Thanks to early funding through CIHR's Regional Partnerships Program (RPP)*, Dr. Patrick Parfrey and his team were able to make substantial strides in the research that would lead to the discovery of the gene for ARVC5. From 2001-2004, Dr. Parfrey was the Principal Investigator of an RPP grant to examine the clinical and genetic epidemiology of ARVC5.

"The RPP grant was a critical piece of funding," notes Dr. Parfrey, who is a University Research Professor at Memorial University of Newfoundland, a staff nephrologist, and Associate Dean for Clinical Research. "It had a substantial impact. The grant funds were used to hire the key person, Cathy Hodgkinson, a research genetic counselor who identified all the Newfoundland family members at risk and collected extensive clinical information. We were able to connect that clinical information and really understand what it meant to have the 'defect.' Dr. Sean Connors, one of the co-investigators on the RPP grant, implanted defibrillators in people (particularly men) who had a high risk of having the genetic mutation and ended up saving lives. We were also able to collect a 'DNA bank', and that bank led to the identification of the genetic trigger that leads to ARVC5. It wouldn't have been possible without RPP."

From 2005-2008, Dr. Parfrey worked with Dr. Terry-Lynn Young and Dr. Sean Connors as the Principal Investigators of a new CIHR grant to continue their hunt for the ARVC5 gene and to build on the progress that was made through the RPP funding. In early 2008, the proud team announced that Dr. Terry-Lynn Young's lab had found the exact location of the gene on Chromosome 3.

Unlike most gene discoveries, this one has immediate clinical applications: Now that the ARVC5 gene has been identified, a simple blood test can reveal whether or not a person carries the genetic mutation. Those with the mutation, which turns out to be a single 'typo' in a string of 400 genetic letters, can be identified and can have defibrillators implanted near the collarbone. When these devices detect an irregular heartbeat or arrhythmia, an electrical shock restores a healthy heartbeat, effectively saving the patient's life. Those without the mutation can also be identified – with certainty – and can finally know relief from "the fear" that had kept them wondering if they would see another day.

"The sudden cardiac death project is a successful example of research deriving from a collaborative approach in which genetic counsellors, molecular geneticists, clinical epidemiologists, cardiologists, philosophers, and health policy experts have functioned as a team and coalesced around trying to solve a major clinical problem," says Dr. Parfrey, who also emphasizes how proud he is that the work on identifying the ARVC5 gene was all done in Newfoundland through the hard work of multidisciplinary teams. "This is a model for future genetic work."

Described by his peers as "phenomenally productive," Dr. Parfrey's honours include a CIHR-RPP Distinguished Scientist Award** (2000-2004) and the Medal for Research Excellence from the Kidney Foundation of Canada (2002); he was also named an Officer of the Order of Canada (2004), the country's highest lifetime achievement honour.

Dr. Parfrey's expertise actually spans three distinct areas: kidney disease, genetics, and cardiovascular research. His recognition of the potential benefit of multidisciplinary research has led to important collaborative studies. For example, from 2002-2007, Dr. Parfrey was one of the Principal Investigators with CANPREVENT (The Canadian Prevention of Renal and Cardiovascular Endpoints Trial). This study was designed to test whether a nurse co-ordinated clinic involving a medical kidney specialist can reduce or delay the onset of advanced kidney disease and heart and blood vessel problems (such as heart attack, stroke, and death) to a greater extent than usual care. In addition, the multidisciplinary study addressed issues of costs associated with care and illness, and also examined the nature of the care provided by professionals to understand best practices for achieving better health outcomes.

Dr. Parfrey notes that it wasn't until about 2000-2001 that he started to venture into large scale team science. He joined the Faculty of Medicine at Memorial University in 1984, and between 1984-2000 he was able to garner approximately $7M in research funding. Since 2000, he has been able to obtain approximately $28,930,000 in research funding.

"I believe that a lot of that growth was stimulated by the RPP," he explains. "As a clinical epidemiologist, the CIHR-RPP Distinguished Scientist award and the RPP operating grant provided me with protected time to conduct research and to progress in my research career. It was the push from RPP that let me stay competitive."

*RPP is designed to help build research capacity and support excellent health research in the less populous regions of Canada.

**Note: The Distinguished Scientist funding program has been discontinued. The final intake for Distinguished Scientist applications was September 1999.