Spotlight on Québec
By Julie Langelier
Translational research: a successful model How PCSK9 went from an enzyme discovered in the lab to a drug target that could revolutionize the way we treat high cholesterol levels
T
he “bench to bedside” approach, also known as translational research, denotes the transfer of knowledge obtained in basic research laboratories into the development of new methods to diagnose, treat and prevent diseases in patients. This increasingly important research model contributes to improving health by accelerating the application of scientific breakthroughs to patients in need. In 1967, the IRCM (Institut de recherches cliniques de Montréal) became the first independent academic research centre in Quebec to unite basic and clinical researchers under one roof, thereby establishing the ‘bench to bedside’ philosophy that has been largely responsible for its success. At the time, IRCM founder Dr. Jacques Genest was determined to build clinical research departments in way that would promote frequent and close interactions between basic scientists and clinicians, as they were too often dispersed in various sections of a hospital or university campus. Thus, the IRCM was born from the notion that the future of Quebec medicine was in the hands of doctors who could most effectively treat patients by combining their clinical skills with the knowledge acquired from biomedical research. “The fundamental idea was to take a problem at the bedside, bring it to the lab to find a solution based on scientific insight, then apply that solution back to patients,” says Tarik Möröy, PhD, the IRCM’s president and scientific director. “We continue to respect these founding principles at the IRCM and, to do this, we foster an environment in which scientists can conduct first-rate research projects in close collaboration with practising clinician-scientists who provide the
“We discovered that the PCSK9 enzyme leads to an accumulation of LDL cholesterol (or bad cholesterol) in the blood and contributes to the growth of plaque that eventually blocks arteries.” — Nabil G. Seidah
necessary bedside knowledge and input.” Imitated by numerous other research centres, the IRCM’s approach is proving to be extremely relevant and has led to several important discoveries, including that of an enzyme called PCSK9, the ninth member of a family of proteins called proprotein convertases, which were discovered at the IRCM in the early 1990s. IRCM researchers Nabil G. Seidah, PhD, and Michel Chrétien, MD, are pioneers in the field of research on proprotein convertases and, in 2003, were the first to describe PCSK9. The same year, Dr. Seidah’s team, in collaboration with French researchers, discovered that PCSK9 plays a key role in regulating blood cholesterol levels. This was one of the most exciting discoveries in cardiovascular research in the last decade. “We discovered that the PCSK9 enzyme leads to an accumulation of LDL cholesterol (or bad cholesterol) in the blood and contributes to the growth of plaque that eventually blocks arteries,” explains Dr. Seidah, who won the 2011 Wilder-Penfield Prix du Québec for his research on proprotein convertases. “Following numerous observations, we found that inhibiting the function of PCSK9 can significantly lower LDL cholesterol levels.” In addition, Dr. Chrétien identified three French Canadian families whose members have a uniquely potent PCSK9 mutation. “This mutation causes their blood cholesterol levels to decrease to levels unattainable by drug treatments alone, and these subjects have no obvious side effects,” mentions Dr. Chrétien. Lowering blood cholesterol is important as Michel Chrétien
“This mutation causes their blood cholesterol levels to decrease to levels unattainable by drug treatments alone, and these subjects have no obvious side effects.” —
Biotechnology Focus / August/September 2014
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