September 15, 2009 (Vol. 29, No. 16)

Canada’s “Little City” Has Made a Big Investment in Biotechnology and It Seems To Be Paying Off

Quebec, the “little city” on the St. Lawrence River—little compared to its big sister 60 miles to the southwest, Montreal—is not only home to a wealth of history, spectacular scenery and architecture, and a taste of European culture, but is also becoming a regional hub of excellence in biopharmaceuticals and life sciences research, vaccines, diagnostics, optics/photonics, and nutraceuticals.

Investment in high-tech research and commercial ventures is on the rise in Quebec City, a region with 1 million inhabitants, 4.8% unemployment, and such an abundance of jobs in the technology sector that local companies participate in international job fairs to attract suitable applicants.

Quebec City’s 15 million square foot Metro High Tech Park is about 88% occupied and continually adding new companies, including names well-known in the pharma/biotech sector such as GlaxoSmithKline, Anapharm, and BD Diagnostics, a segment of BD. It is currently home to more than 90 companies and 5,000 employees.

POLE Québec Chaudière-Appalaches is the economic development agency driving entrepreneurial growth, innovation, investment, and job creation in the Quebec region. Led by CEO Carl Viel, POLE provides expertise and support in establishing strategic partnerships, technology transfer, recruitment, export opportunities, and skills development and training; it also organizes regional and international forums and expositions. The agency works closely with Investissement Quebec to identify suitable sites, capital sources, loans, tax incentives, and other financial services for commercial development and expansion.

Tissue phantoms manufactured by INO (National Optics Institute)

Leveraging Expertise

Optics/photonics is an area of particular expertise in Quebec, with a host of researchers developing technology applications in biophotonics. At the National Optics Institute (INO), for example, researchers have developed “phantoms,” which are materials that mimic the absorption and scattering properties of living tissues, such as breast tissue, with and without a tumor that allows scientists to design imaging and detection techniques without having to work with actual tissue samples. INO is also developing a miniaturized, sheathless flow cytometer capable of single-cell analysis and an optical technique to measure local oxygen concentration in patients undergoing photodynamic therapy for cancer.

At the forefront of applying photonics and nanotechnology to neuroscience research is Yves De Koninck, Ph.D., head of the cellular and molecular neurosciences unit of the Centre de Recherche of Laval University Robert-Giffard (CRULRG). Dr. De Koninck’s research focuses on identifying the cause of chronic pain, and his group has discovered an ion pump dysfunction in the nervous system that disrupts neurotransmitter signaling and represents a promising new lead for novel drug target identification. Dr. De Koninck recently cofounded Chlorion Pharma to explore the commercial applications of these discoveries.

CRULRG collaborates with McGill University and Laval University’s Center for Optics, Photonics, and Lasers to apply photonics to biological applications. For example, researchers are using light to look inside cells without disrupting their activity and specifically to image individual neurons and neural circuits as they respond to sensory information, leading to a better understanding of the mechanisms that underlie a coordinated neuronal response to a stimulus, they hope.

Other research projects at CRULRG focus on neuronal switching to treat brain trauma and neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases, and the use of photonics to track the movement of stem cells implanted in the bone marrow of live mice.

Paul De Koninck, Ph.D., young investigator of the Canadian Institute of Health Research, is using optical technology to study how nerve cells communicate. He uses lasers to image cultured nerve cells in a 2-D network and to study how they regenerate and form synapses. By tracking fluorescently tagged proteins his team can watch individual synapses form from dendrites, visualize the plasticity of neurons, study remodeling and communication between synapses, and use optics to track neurotransmitter receptors in and out of synapses. By tagging receptors at the cell surface with functionalized quantum dots, it is possible to resolve single molecule events in situ.

Armen Saghatelyan, Ph.D., Canada research chair in postnatal neurogenesis, uses optics/photonics tools to track neural progenitor cells in real time as they migrate to specific areas of the adult brain. The goal is to learn how to control this migration and to divert the cells to damaged areas of the brain where progenitors would not normally migrate.

Daniel Côté, Ph.D., Canada research chair in biophotonics, develops optical approaches for cellular imaging of the nervous system in live animals. He has created a feedback-controlled hardware device that guides a microscope or laser to move in sync with an animal, and his group is using this device to enable in vivo, label-free optical histology to image myelin and the development of multiple sclerosis in mice.

Researchers at the Center for Optics, Photonics, and Lasers (COPL) at Laval University are working at increasing the efficiency and range of FRET for imaging and biosensing applications.

Vaccines and Molecular Diagnostics

The Centre de Recherche en Infectiologie (CRI) of Laval University has given rise to several commercial ventures, including two diagnostics companies, Infectio Diagnostic (now BD Diagnostics) and GenePOC; instrumentation developers Autogenomics and Silicon Kinetics; as well as Gealth, which developed the vaginal microbicide Invisible Condom® to protect women against HIV infection; Folia Biotech, which is developing vaccines against typhoid fever, influenza, and hepatitis C; Diapedex, a company pursuing R&D on immunomodulatory drugs to control inflammation; and Génocéan, which is applying metagenomics technology to the study of environmental microbiology.

Michel Bergeron, M.D., founding director of CRI describes the next generation of diagnostic products in development as microfluidic centripetal devices, which will automate all of the steps needed for sample preparation, PCR-based DNA amplification, and detection of infectious agents and will be used at the point of care.

Vaccine researchers at CRI are focusing on developing novel adjuvants as well as preventive strategies for leishmaniasis and HIV. Additional research programs target the diagnosis, pathogenesis, and treatment of viral respiratory infections, host-pathogen interactions induced by bacteria, viruses, and protozoa, and the emerging science of glycobiology and the immunomodulatory role of glycoproteins.

DiagnoCure, which develops diagnostic tests and provides cancer-specific laboratory services, is awaiting the results of a large-scale clinical trial of its PCA3 marker for prostate cancer. DiagnoCure has successfully launched a commercial product on the U.S. market—the Previstage™ GCC molecular colorectal cancer staging test.

Previstage detects guanylyl cyclase 2C (GCC), a marker expressed by colorectal tumors that is predictive of recurrence risk, the firm says. An NIH-sponsored study published in February demonstrated a significant association between GCC expression and colorectal cancer prognosis in patients whose lymph nodes showed no signs of metastatic disease on histologic examination. GCC expression in the lymph nodes indicates the presence of cancer cells and is an independent marker of time to recurrence and reduced disease-free survival. The assay can reportedly detect a single cancer cell in up to 10 million normal cells. 

About 27% of the “node-negative” patient specimens tested using Previstage are found to be positive for metastatic disease. The company expects interim data in 4Q09 from a five-year prospective study to evaluate whether GCC can detect cancer recurrence following curative surgery or chemotherapy.

DiagnoCure licensed the commercialization rights to its PCA3 urinary marker for prostate cancer to Gen-Probe.

The Progensa® PCA3 assay is used to help determine the need for a repeat biopsy in men with an elevated PSA level and an initial negative biopsy result (approximately 75% of prostate biopsies following elevated serum PSA readings are negative). Gen-Probe’s FDA submission will follow completion of an ongoing 500-man pivotal clinical study.

DiagnoCure acquired the rights to a family of molecular markers called the Shc proteins, and the company is developing Shc protein assays for use in predicting aggressiveness/recurrence risk and response to chemotherapy in five main tumor types, including breast and colon. John Schafer, president and CEO of DiagnoCure, recently reported that at mid-year DiagnoCure had about $20 million in the bank and was exploring strategic alliances in Europe and Asia.

BD Diagnostics, through its BD GeneOhm™ platform, is developing nucleic acid-based diagnostics for the detection and identification of infectious organisms, particularly drug-resistant strains infecting patients in healthcare settings.

BD acquired GeneOhm Sciences in 2006, which had previously acquired Infectio Diagnostics, a spinoff from the Infectious Diseases Research Center at Laval University Hospital. BD’s product portfolio includes five rapid, PCR-based assays for detecting Group B Streptococcus, methicillin-resistant Staphylococcus aureus (MRSA) in nasal specimens, C. difficile toxin B gene in stool specimens, and vancomycin-resistant Enterococcus, and for differentiating Staphylococcus aureus and MRSA in positive blood cultures.

In May 2009, BD announced an agreement with HandyLab, to commercialize the BD GeneOhm assays on a new automated BD MAX™ platform based on HandyLab’s Jaguar instrument. The bench-top Jaguar system provides fully automated clinical sample preparation, nucleic acid extraction, and microfluidic real-time PCR amplification and detection. 

Several commercial ventures have been spun out of Laval University in Quebec, including Infectio Diagnostic, which merged with GeneOhm in 2005.

Functional Foods

The Institute of Nutraceuticals and Functional Foods (INAF) at Laval University studies the relationship between foods, food components, nutrition, and health. Under the leadership of director Yves Pouliot, Ph.D., INAF focuses on identifying food components with potential use as nutraceuticals for disease prevention and improving quality of life. Researchers perform genomic studies and evaluate animal models to understand the effects of food intake, energy balance, and dieting on disease risk factors.

Industrial research chair Denis Roy, Ph.D., leads a group at INAF focused on decoding the microbial populations in cheese. Dr. Roy describes cheese as “a living organism,” and he is applying metagenomics techniques to study the DNA and RNA extracted from cheese and to characterize microbial diversity and activity.

By tracking microbial populations throughout the cheese-production process, the researchers aim to develop techniques for controlling maturation and the resulting flavor and quality of cheeses and to be able to predict the quality, safety, consistency, and acceptability of cheese products.

Economic Indicators and Incentives for Doing Business in Quebec City

  • Unemployment (1H09) = 4.8%
    (vs. 8.3% for Quebec Province and 8.0% for Canada)
  • Jobs (1H09) = +2,700 compared to 1H08
  • GDP (avg annual growth 1Q07–09) = 3.3% (vs. 0.7% for Quebec Province and 0.5% for Canada)
  • Per capita personal income growth (1Q07–09) = 4.9% (projected 2.8% in 2010)
  • Capital investment growth (2004–2009) = 47.4% (vs. 24.8% for Quebec Province)
  • Typical business start-up and operating costs = $14.06 million (vs. an average of $14.35 million for Canada and $15.19 million for the U.S.)
  • Effective tax rate for manufacturing companies = 30.90% (vs. 44.41% for New York and 40.75% for California)
  • Refundable tax credits include: 17.5% of R&D salaries paid in Quebec; 35% of eligible R&D expenditures at accredited research centers
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