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R&D News
www.laboratoryfocus.ca
NOVEMBER 2012 Volume 16, Number 6
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2012 Readers’ Choice Awards
Page 10
R&D News ......................... 1 Appointments .................... 6 Pharma Notes.................... 7 New Products .................. 15 Calendar .......................... 17 Career Spotlight............... 18
DR. MICHAEL KELLY NAMED SASKATCHEWAN RESEARCH CHAIR IN CLINICAL STROKE RESEARCH
Saskatoon brain surgeon and medical researcher Dr. Michael Kelly has been awarded the Saskatchewan research chair in clinical stroke research to pursue his work in the operating room and at the Canadian Light Source synchrotron to advance understanding of strokes and improve prevention and treatment.
“The creation of this chair in clinical stoke research increases our health research capacity and enables collaboration toward Saskatchewan solutions in dealing with strokes, which have a devastating effect on individuals and their families,” said Rob Norris, Saskatoon Greystone MLA on behalf of Health Minister Dustin Duncan.
The chair will provide $1 million over five years, jointly funded by three Saskatchewan organizations –- the Heart and Stroke Foundation (HSF), the Saskatchewan Health Research Foundation (SHRF) and the University of Saskatchewan (U of S). The U of S will provide an additional $200,000 for equipment and personnel costs, as well as providing protected research time and salary.
The Saskatoon Health Region is also providing contributions through additional access to equipment, facilities and personnel. ”The world of stroke treatment has radically changed in the past decade, largely due to a focus on stroke research,” said Lorie Langenfurth, CEO of the Heart and Stroke Foundation. “But this is still a devastating condition that affects 50,000 Canadians every year. Dr. Kelly’s work will bring us that much closer to turning the tide on stroke.”
Kelly’s research program will use synchrotron imaging to trace how stem cells move through the brain after a stroke. He will also test the properties of stents – expandable mesh tubes placed inside blood vessels – with a view to improving these and similar medical devices. These research activities are expected to contribute greatly to knowledge and awareness of stroke care, treatment and prevention.
The Saskatchewan research chairs program aims to attract, support and retain top-quality research leaders who are working in a provincial priority area and who contribute to capacity building and knowledge sharing in those areas.
NEWS
Baxter International Inc. and MaRS Innovation, a centre of excellence for commercialization and research, have entered into a strategic partnership to commercialize early-stage technologies that present innovative methods in therapeutics and drug discovery technologies.
Baxter and MaRS Innovation will identify investment opportunities emerging from well-validated scientific research discoveries within MaRS Innovation’s 16 member institutions, including the University of Toronto and its nine affiliated teaching hospitals. Baxter will provide up to U.S. $1 million in funding over a three-year period to support promising individual projects based on their positive due diligence, which will be leveraged with financial support from MaRS Innovation to accelerate the development and validation of healthcare technologies within the largest academic cluster in Canada.
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INNOVATIVE NEW DEFIBRILLATOR OFFERS ALTERNATIVE FOR REGULATING HEARTBEAT
Dr. Pablo Nery and Dr. David Birnie from the University of Ottawa Heart Institute (CNW Group/Ottawa Heart Institute, University of Ottawa).
A new ground-breaking technology was recently used at the University of Ottawa Heart Institute (UOHI) where two cardiologists, Dr. David Birnie and Dr. Pablo Nery, implanted a new innovative leadless defibrillator, the subcutaneous implantable cardioverter defibrillator (S-ICD), in an 18-year-old patient. Under Health Canada’s special access program, this was only the third time this new type of ICD had been implanted in Canada.
Conventional defibrillators, known as transvenous defibrillators, are implanted with wires, called the leads, that snake through veins into the heart. When the defibrillator identifies any dangerous heartbeat, it delivers a shock through the wires to return the heart to its normal rhythm and allows it to get back to pumping blood steadily throughout the body.
Not all patients are suitable for a conventional defibrillator. In some with congenital heart problems, there is no way to advance the leads into the heart through the veins. Also, those wires may pose a danger due to the risk of blood clots or infection. Patients often have to undergo a more complex and invasive surgery to attach the leads to the outer layer of the heart muscle in order to benefit from the use of a defibrillator.
Conventional ICDs use leads that run from the device through major veins to an anchor point in the heart. These transvenous leads can cause problems in the long term. Despite decades of design improvements, leads can malfunction, break or stop working. Known as lead failure, this results in either inappropriate shocks or lack of proper regulation of the heartbeat. What’s worse is that failed leads often must be removed, which poses serious risks to the patient.
What makes the new device special is that it is entirely subcutaneous. No part of it actually touches the heart. Instead, an electrode is implanted just under the skin near the heart. The defibrillator is connected to the electrode, and monitors the heartbeat at all times. If needed, it delivers a shock to the heart muscle to restore its normal rhythm.
The goal of the subcutaneous ICD is to potentially reduce or eliminate these problems. “The subcutaneous ICD provides effective therapy for patients who are either not eligible for or are at high risk with a traditional ICD. Such patients may now be able to receive protection from a subcutaneous ICD without the risks associated with the standard leads,” explained Dr. Nery.
That made the 18-year-old recipient of the S-ICD at the Heart Institute a perfect candidate. “The S-ICD offers advantages for particular patient sub-groups,” said Dr. Nery. “This technology is now an alternative for young patients, in part because lead extraction can be avoided down the road.”
Another advantage is more aesthetic in nature but, nonetheless, important for young people. A conventional transvenous defibrillator sits on the front on the chest, just under the collarbone, and is easy to see. The S-ICD, in comparison, is implanted to the side, under the patient’s arm, and with a much smaller incision than with the transvenous defibrillator. That, said Dr. Nery, is an important consideration for many patients in terms of body image and quality of life.
NEWS
INDUSTRY AND ACADEMIA COLLABORATE IN ANTI-TB VACCINE DEVELOPMENT
Dalton Pharma Services and the University of Guelph are collaborating on the development of an anti-tuberculosis (TB) vaccine. Initiation of the program was made possible through government funding directed at applied research.
The vaccine will be jointly developed at the University of Guelph and Dalton under the direction of professor Mario A. Monteiro, who is a world leader in microbial polysaccharide discovery and the development of polysaccharide-based vaccines. Dalton will scale up and manufacture the conjugate vaccine under GLP for proof of concept studies in an animal model.
“This collaboration is a perfect fit for our long term business development strategy in the vaccine field”, said Peter Pekos, CEO of Dalton. “A vaccine against TB is one of the world’s most sought after vaccines. Successful commercialization would result in a potential blockbuster product that Dalton will manufacture in Canada. Industry, government, and academia will work together creating highly skilled jobs and further strengthen our capacity for innovative development in the vaccine sector.”
Commented professor Monteiro, “I am delighted to embark on this project with Dalton, on the leading edge of development of the vaccines to treat diseases that cause considerable suffering around the world.”
“Tuberculosis,” continued professor Monteiro, “causes more deaths than any other infectious disease. About two billion people are infected with the TB bacteria, Mycobacterium tuberculosis. Each year, eight million people develop active TB, and two million die. Although the world’s poorest countries have the highest overall incidence of active TB, some segments of North American society have even greater rates. The challenges posed by this disease have been increased by the emergence of multi-drug resistant strains. Current treatments for MDR-TB involve very long periods of intensive drug therapy, which are accompanied by side effects many patients find unbearable, and often fail.”
The strategy used for the anti-TB vaccine program of Dalton and U of G is to develop an initial vaccine which is effective against Mycobacterium bovis, the agent responsible for tuberculosis in cattle and lions. Previous studies have shown that M. bovis and the human agent M. tuberculosis share similar polysaccharides. The polysaccharide-based M. bovis vaccine will be constructed using technology developed by professor Monteiro and will be evaluated in a lion animal model through an arrangement already in place with veterinary expertise at the Timbavati Nature Reserve in South Africa. A successful outcome will lead to a vaccine treatment for animal TB, and will provide a solid platform for the development of a human anti-TB vaccine.
NEWS
Continued from page 2
“We value this opportunity to partner with Ontario’s leading universities and research institutions through MaRS Innovation to advance innovative technologies and product platforms that have the potential to improve outcomes for patients, while contributing to reducing the total cost of care,” said Norbert G. Riedel, chief science and innovation officer for Baxter.
“By bringing together pre-eminent researchers and institutions from across Ontario with investments and expertise from organizations like Baxter, we can incubate and hopefully develop new therapeutic concepts in areas of high unmet medical need,” said Michael Oliver, general manager for Baxter Canada.
“This partnership is another testament to the excellence in the innovation pipeline that MaRS Innovation’s members represent,” said Dr. Raphael Hofstein, president and CEO of MaRS Innovation. “Baxter is a significant global player in delivering healthcare technologies. We are excited that they view the Ontario ecosystem as a hub of innovation for development and commercialization. Partnerships like this one represent a significant opportunity to not only attract financial resources, but also expertise and market validation for technology development.”
SCIENTISTS FIND WAY TO CONTROL SUGARS
L to R: Mario Pinto, Eric LeGresley and Kyle Greenway
A study co-led by Simon Fraser University has found that the intestinal enzymes responsible for processing starchy foods can be turned on and off, helping to better control those processes in people with Type 2 diabetes.
The process, called “toggling,” was discovered in the lab of SFU chemist Mario Pinto, who has designed inhibitors capable of regulating each of the four starch-digesting enzymes known as alpha-glucosidases. It could lead to several solutions for diabetics and those prone to obesity.
Three of these enzymes are responsible for generating glucose from starch, each in different ways. A fourth enzyme breaks down sucrose, also giving glucose. Occasionally one or more of the enzymes is missing, which also affects how glucose is created, Pinto explains.
“We wanted to determine whether we could control the release of glucose when starch is broken down in the body,” says Pinto, whose work included characterizing each of the four enzymes.
Working with a consortium of scientists co-led by Purdue University’s Bruce Hamaker, a professor of food science, Pinto says the inhibitors were found to selectively inhibit the enzymes and control starch breakdown, meaning it could be possible to provide the missing enzymes or develop new starches that will digest properly with the enzymes they do have.
“It’s all about control and using the molecular information we have to control those enzymes,” he says.
“Selectively inhibiting the enzymes offers the possibility of regulating and directing the release of glucose,” says Pinto, noting the consortium of scientists approached the problem from chemical, structural, molecular and cellular perspectives.
When enzymes are missing – a common characteristic of a rare disease known as CSID – Pinto says it may be possible to administer one, and design foods in certain ways that other enzymes can break down.
“This is a powerful piece of knowledge,” adds Pinto, noting that in the future it may be possible to control the exact delivery of glucose at different points in the small intestine.
The discovery could result in the control of blood glucose for Type 2 diabetes as well as other conditions. The findings were published in the Journal of Biological Chemistry.
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for more information or to apply go to www.chem-tech.ca/cct PROOF CENTRE PARTNERS WITH MRM PROTEOMICS TO BRING NEW TESTS TO CLINIC
The Centre of Excellence for the Prevention of Organ Failure (PROOF Centre) and MRM Proteomics are collaborating to bring new diagnostic blood tests to the clinic they hope will help clinicians manage patients with heart, lung and kidney disease more effectively.
MRM Proteomics is a CRO which specializes in the quantification of proteins in complex biological fluids such as blood and urine using Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). The companies PeptiQuant™ MRM assays for example allow for the absolute quantification of hundreds of proteins at a time from a single drop of blood. As part of the collaboration, the PROOF Centre’s computational pipeline will be applied to guide the experimental design, and data quality control and analysis needed for the identification of protein signatures that can be used with other molecular signals to indicate heart, lung, and kidney disease. The PROOF Centre will also support the analysis process from front-end experimental design to downstream statistical and biological analysis.
“Our organizations’ offerings are clearly complementary in the field of protein biomarker discovery and validation.” said Andrew Munk, president and CEO of MRM Proteomics. “The discovery, validation and implementation of biosignatures are complex processes. Partnering with the PROOF Centre will provide our customers with access to the PROOF Centre’s internationally recognized computational tools and capabilities to optimize the design and analysis of their mass spec based proteomic biomarker studies.”
NEWS
FIRST SUCCESSFUL CLINICAL TRIAL TO PROTECT THE BRAIN FROM DAMAGE CAUSED BY STROKE
A team of Canadian scientists and clinicians, led by Dr. Michael Hill of the Calgary Stroke Program at Foothills Medical Centre and University of Calgary’s Hotchkiss Brain Institute (HBI), have demonstrated that a neuroprotectant drug, developed at the Krembil Neuroscience Centre, located at the Toronto Western Hospital, protects the human brain against the damaging effects of stroke.
The study, “Safety and efficacy of NA-1 for neuroprotection in iatrogenic stroke after endovascular aneurysm repair: a randomized controlled trial,” published in The Lancet Neurology, was conducted concurrently with a laboratory study published in Science Translational Medicine, that predicted the benefits of the stroke drug.
This landmark clinical trial was a randomized, double blinded, multi-centre trial that was conducted in Canada and the U.S. The study evaluated the effectiveness of NA-1[TatNR2B9c] when it was administered after the onset of small strokes that are incurred by patients who undergo neurointerventional procedures to repair brain aneurysms. This type of small ischemic stroke occurs in over 90 per cent of aneurysm patients after such a procedure, but usually does not cause overt neurological disability.
In the clinical trial, patients were randomized to receive either Tat-NR2B9c or placebo. Those treated with Tat-NR2B9c showed a reduction in the amount of brain damage sustained as a result of the aneurysm repair procedure. Also, in patients who had ruptured brain aneurysm, which comprise a population of patients at very high risk of neurological damage, those treated with Tat-NR2B9c all had good neurological outcomes, whereas only 68 per cent of those treated with placebo had good outcomes. “The results of this clinical trial represent a major leap forward for stroke research,” said Dr. Hill. “There have been over 1,000 attempts to develop such drugs, which have failed to make the leap between success in the lab and in humans.”
“This clinical trial is, to our knowledge, the first time that a drug aimed at increasing the resistance of the brain to stroke has been shown to reduce stroke damage in humans. No efforts should be spared to develop it further,” said Dr. Michael Tymianski, who oversaw the development of TatNR2B9c from its invention in his lab, through to clinical trials.
Currently, t-PA is the only widely approved acute stroke therapy. It works by unblocking the arteries to the brain. However, this treatment is only beneficial for a portion of stroke victims. It also has serious potential for side-effects, including bleeding in the brain.
“Through our lab research and clinical trial, we now have a better method of predicting whether a stroke drug may be effective in humans and we now have the evidence that there is a neuroprotectant that can prevent damage in the brain caused by reduced blood flow,” said Dr. Tymianski, inventor of NA-1 and one of the study’s authors. “The benefits of this can be explored not only for stroke, but for other conditions such as vascular dementia.”
TYING OUR FATE TO MOLECULAR MARKINGS
A Simon Fraser University physicist has helped discover that understanding how a chemical mark on our DNA affects gene expression could be as useful to scientists as fingerprints are to police at a crime scene.
Eldon Emberly along with colleagues at the University of British Columbia and Standford University cited proof that variable methylation, a chemical mark on our DNA, is predictive of age, gender, stress, cancer and early-life socioeconomic status within a population. DNA that is methylated in our genomes is known to affect whether genes are turned on or off. Gene expression predicates several attributes linked to our identity, such as gender, ethnicity, age and health.
Emberly and his colleagues measured methylation from DNA in the white blood cells of 92 people aged 24 to 45. Emberly’s lab helped to mine the resulting data sets for correlations between variation in the chemical mark and variable social, psychological and physical traits in the subjects.
The results demonstrated that those who had experienced childhood poverty had a different methylation level from those who hadn’t. This was despite the fact everyone in the cohort had achieved the same socioeconomic status later in life. That meant that early-life environment had left a detectable molecular mark on an individual’s DNA.
The correlation between methylation and gene expression was complex because it wasn’t always predictable but there was one connection of particular note says Emberly.
Emberly says this study’s discoveries raise interesting questions, as the connection between methylation and some traits, such as smoking and alcohol consumption, was weaker than expected or non-existent.
“We’re now investigating whether methylation variation in different types of tissue is more predictive of some trait,” adds Emberly.
Pau Farre, a master’s of science student in physics under Emberly’s supervision, is doing a statistical analysis of the variability in methylation across tissues.
