A recent trip to Canada's biotech sector in Saskatoon revealed a raft of drug-related innovations. Kirsty Osei-Bempong reports
The smaller the business, the bigger the risks taken is a belief that holds weight when applied to the network of small biotech firms dotted across Saskatoon in Saskatchewan.
The city is home to about a third of Canada's agricultural biotechnology companies, whose focus spans from plant-made pharmaceuticals (PMPs) right through to vaccine development based on animal disease research. In some cases, these firms are challenging views on existing methods of drug manufacture and delivery, and producing interesting results.
Take the Vaccine and Infectious Disease Organization (VIDO), which, together with the University of Saskatchewan, is close to completing construction of the 145,000ft2 International Vaccine Centre (InterVac).
Set for completion in 2010, this C$140m (Euro 92.4m) centre is expected to be the largest bio safety containment level-three vaccine research facility in Western Canada. As well as being one of a few centres in the world able to handle and use large-scale animals in research, the facility will play a key role in developing new drug delivery methods for humans and animals, using the Canadian Light Source synchrotron. The synchrotron can be used for a variety of applications, including biomedical imaging, cancer research therapies and vaccine development.
Creation of the facility is significant in that it pushes the boundaries of drug and vaccine development. Instead of using the accepted "mouse model" route for testing the efficacy of drugs for humans, larger animals are believed to make better models because they share many of the same diseases.
And when you are aware that about three-quarters of new diseases in humans arise from animals, according to VIDO, studying animals and improving their health makes sense. "The world is slowly coming round to the idea but it's quite a battle," says VIDO associate director of research Dr Andrew Potter, who led the development of the first E. coli O157:H7 cattle vaccine two years ago.
The vaccine, which VIDO developed in partnership with the University of British Columbia, the University of Saskatchewan and Bioniche Life Sciences in Ontario, sought to protect humans from contaminated food and water. Although E.coli does not adversely affect cattle, it can cause illness and even death when it enters the human food chain. "The vaccine prevents the bacteria [in cattle] from attaching to the intestine," says Potter. "This in turn prevents its ability to remain - and reproduce - in the body."
Since then, VIDO has used its 33-year history of specialising in animal disease to develop other vaccines that straddle the human and animal line. Whooping cough (pertussis) is one project underway in piglets, and forms part of VIDO's neonatal immunisation programme. The organisation has also shown an interest in the "immunological castration" of animals - a process that is being explored by Star Bio-technology and that could have future implications for humans.
"The castration of animals is a severe way of controlling reproduction," says Potter. "Developing a vaccine that would castrate animals immunologically and that is also totally reversible, has obvious benefits."
needle-free vaccination
VIDO is also exploring improved methods of delivering vaccinations, such as needle-free administration in cattle. The technology delivers a stream of high-pressure fluid directly through the skin, which is claimed to be cost-effective and more practical than the traditional approach.
One advantage the method offers is that the dose of vaccine needed to induce protective immunity is much reduced and animals do not react during vaccination, indicating there would likely be fewer vaccine failures when processing large numbers of animals. Once again, this process of drug delivery could be developed for use in humans and could mirror drug delivery processes used in the past. According to Potter, transnasal vaccines using bamboo sticks to deposit treatment were used in China in the 1400s.
VIDO is not alone in its use of innovative vehicles. Private biotech company Prairie Plant Systems (PPS) claims to be the only one of its kind using plants as "biofactories" to manufacture drugs underground.
perfect environment
According to president and ceo Brent Zettl, the underground biosecure growth chamber in a mine near Flin Flon Manitoba, is 365 metres below ground and provides the perfect environment to grow PMPs. The enclosed nature of the plants" environment means that water and carbon dioxide levels can be controlled, plants are not exposed to pathogens or fluctuations in temperature, and complete genetic containment can be achieved.
"Good manufacturing practices (GMP) require real consistency of batch product," Zettl says. "If plants are on the field, they are impacted by the environment and that affects the consistency you get."
The company was first awarded the medical marijuana contract by the Canadian health board Health Canada in 2000 and has since opened a second pharmaceutical-approved growth chamber in White Pine, Michigan, US.
"Using plants to produce drugs was not possible even 10 years ago but technology has moved so far in understanding the DNA of plants and diseases that we can now use nature to produce safe and effective drugs and vaccines," says Dr Brandon Price, a PPS board member. The PMP market, although small, is estimated to be worth US$125bn (€84m) a year globally, according to PPS.
Keen to bolster this success, the company is in involved in several projects, including a contract from Health Canada to produce a glycoprotein B (gB) of human cytomeglovirus (HCMV). HCMV infection is a common cause of morbidity in HIV-positive patients, particularly in the later stages of AIDS.
Its most recent venture is in a Hepatitis-C (HCV) project aimed at creating a protein in plants that will act as vaccine for HCV. VIDO is using its expertise to isolate and identify the core HCV protein, while the Plant Biotechnology Institute in Saskatoon, is involved in the production and testing of the protein produced by a plant.
"There are synthetic drugs in use that attack the virus but they a have limited impact," says Zettl. "If PPS is successful, it will be able to produce economically a core HCV protein that, when administered to patients, could act as a vaccine, preventing the disease instead of trying to cure it."
After expressing the protein in a plant, the plan is to conduct preclinical trials to determine if the protein has the desired vaccinating effect. If clinical activity is demonstrated, PPS plans to partner with a company that either has access to this market or may already have patents on the HCV market to take the product to human clinical trials, and even gain regulatory acceptance for a drug.
chewable softgels
Meanwhile, in the area of nutraceuticals, it is the baby boom generation that is helping to shape growth, according to Bioriginal Food and Science Corp president Joe Vidal.
Driven by a strong desire to maintain a healthy lifestyle, the company is seeing a surge in demand for essential fatty acids (EFAs). Omega-3, -6 and -9 oils, found in plant and marine sources, including tuna, borage (starflower), and conjugated linoleic acid (CLA), help to improve skin function, cognition and have anti-inflammatory properties.
To help companies capitalise on this growing market, Bioriginal has developed a range of flavoured chewable products designed to make the consumption of marine omega 3 supplements more palatable. Using the company's proprietary patented BioBurst encapsulation technology, the anti-inflammatory BioPureDHA (docosahexaenoic acid) has been incorporated into softgel capsules. These come in a variety of fruit flavours and in dosages from 500mg to 1,300mg.
A Chewable Borage Oil softgel range with a natural orange flavour has also been launched and features the trademarked GRAS ingredient called BioAsteri. US-based company Solgar Vitamin and Herb has been granted the sole rights to distribute the product in 40 international health food sectors.
The bio-tour was organised through the Government of Saskatchewan.