A rare disorder is defined as a disorder that affects less than one in 2,000 Canadians. Many are severe, progressive, and/or life threatening conditions, with high mortality rates and devastating impacts on patients, families and society. Although individually rare, collectively, they affect one in 12 persons or 2.8 million Canadians. There are no effective treatments for many of these disorders. However, for many others, if infants or children are diagnosed and treated early enough, they can avoid physical
disability or cognitive delays and live nearly normal lives.

Rare disorders present unique public health challenges. Few physicians are familiar with diagnosing and treating these conditions, which means most patients are undiagnosed, misdiagnosed, or delayed in diagnosis, so they do not get timely
access to treatments even when therapies exist.

There are relatively few therapeutic options – between 7,000 and 8,000 rare disorders have been identified, but there are only 400 effective drug treatments. This situation is expected to change dramatically with hundreds of new therapies in development
and coming to market over the next decade. But without change in our rare disease environment, many of these therapies will not be accessible for Canadian patients. Currently, Canadians tend not to be included in clinical trials and companies are reluctant to bring their drugs to Canada. Approximately half of the rare disease drugs available to patients in the U.S. or Europe have been approved in Canada and only half of these are funded through public drug plans.

Currently, Canada’s regulatory and reimbursement systems present significant challenges to researchers and developers of drugs for rare diseases, also known as orphan drugs. On the federal regulatory side, the review process is about to change.

In October 2012, Health Canada announced their intention to implement an Orphan Drug Regulatory Framework, a review process for orphan drugs that is similar to those of the U.S. and the European Union. Health Canada has indicated that this framework will include tools to improve the quality of knowledge used by provincial and territorial decision-makers and healthcare professionals, provide the opportunity for patient input, encourage transparency and sharing information, and support international collaboration. By harmonizing Canada’s orphan drug regulatory process with those of the U.S. and the EU,
companies will be able to set up clinical trials and to apply to Canada for market approval at about the same time as they do in these other jurisdictions, ultimately reducing delays and increasing the number of new drugs available to Canadians with
rare diseases.

Unfortunately, a federal regulatory framework will not assure equal access across all provinces. Under Canada’s federated model, screening, diagnosis, care and treatment are the responsibility of individual provinces. With an aging population, there is an inevitable increase in both incidence and prevalence of chronic disease, which translates into greater demand for healthcare and greater use of medications. Provinces challenged by healthcare costs that are increasing, on average by seven percent each year, and drug costs that are proportionately rising even faster, have placed more controls on drug prices and restricted access to new drugs.

To those ends, all provinces (except Quebec) have agreed to collaborate on a Common Drug Review (CDR) to assess the comparative effectiveness and cost-effectiveness of new drugs and the pan-Canadian Oncology Drug Review (pCODR) for oncology drugs. Both will soon by operated under one umbrella, the Canadian Agency for Drugs and Technologies in Health (CADTH). Their mandate is to make recommendations to the public drug plans on which drugs to reimburse, under what conditions and, often, at what price. Intended to reduce duplication and improve consistency across formulary listings, the common evaluation methods used by the processes have disadvantaged certain types of drugs resulting in more negative recommendations. These include drugs for small patient populations, first-in-class drugs without comparators, early-market entry drugs for severe or life-threatening conditions, or drugs that primarily impact quality of life, such as pain management or psychological conditions. What is needed is an orphan drug access framework designed specifically to provide access to drugs for
unmet needs as soon as they are approved by Health Canada. Known as managed access schemes, risk-sharing schemes, or  evidence building schemes, they provide appropriate patients reimbursed access to drugs with a monitoring plan that accumulates evidence of safety, effectiveness, and cost-effectiveness over time.  Such schemes are already being used in Canada  and most other countries, and are much more appropriate to rare disease drugs than the CDR or pCODR.

A new step in the process is the pan-Canadian Pricing Alliance (PCPA), which negotiates a single price and listing conditions for a new drug, on behalf of all participating provinces. The final decision about reimbursement, however, is still made by each provincial or territorial government, ostensibly on the basis of budget impact and other factors. Because the latter two steps
are not transparent – the basis for the negotiated price and the reimbursement decision are not publicly available – it is not clear how different jurisdictions arrive at their respective decisions. It remains to be seen whether the PCPA will reduce delays and  improve consistency of access to rare disease drugs.

Finally, many drugs for rare diseases fall outside of the established regulatory and reimbursement pathways, so patient access is evaluated on a case-by-case basis. These include drugs that are not approved in Canada, are used off-label for a rare condition, or are not listed on the drug formulary. Access may be requested through Health Canada’s Special Access Programme only for the named patient and the patient may additionally need to apply to the provincial compassionate or exceptional access programme. These processes are inefficient, costly and time-consuming, for both the patient and the health care system. Designed for urgent, one-off situations, they are not viable mechanisms to ensure Canadians with rare disorders have sustainable access to appropriate therapy in a monitored and timely fashion.

As importantly, getting drug reimbursement and access right for rare diseases will have big payoffs as we move into the era of personalized medicine for more common conditions. Our knowledge about genetic bases for individual differences in large population disorders such as breast or prostate cancer, diabetes, circulatory conditions, and psychiatric disorders such as schizophrenia will result in identifi cation of subgroups defi ned by genotype. What we are learning and pioneering in drug development and access for rare diseases will someday benefit all patients.

Over the past few years, Canada has made remarkable progress in the care and treatment of patients with rare diseases but, frankly, we still lag far behind most developed countries. The implementation of the Orphan Drug Regulatory Framework will have significant impact, but it still lacks some of the provisions that will ensure pharmaceutical and biotech companies bring research and clinical trials to Canada, including a period of market exclusivity for innovative drugs and tax incentives. Moreover, in order to realize the benefits of a regulatory framework, we need to follow the lead of the 27 EU countries in bringing in a national plan for rare diseases.

The Canadian Organization for Rare Disorders (CORD) in collaboration with the Canadian Institutes for Health Research, Genome Canada, BIOTECanada, and Rx&D are developing the framework for a Canadian Strategy for Rare Diseases that will address the definition of rare diseases, research, diagnosis, care and support, and access to treatment. This strategy allows us to consider rare disorders in the context of a broader public health approach and builds upon existing infrastructure, expertise, and programmes. Although Canada has come late to the game, there is an opportunity for us build on existing international experience and knowledge.

Canadians with rare diseases have a right to the same health care as those with more common conditions. A Canadian strategy for rare diseases will help ensure the most effective and cost-effective way to providing that care.

Roche and Montreal-based venture capital firm AmorChem L.P. have entered into a collaboration to discover novel small molecule diseasemodifying therapies for the treatment of myotonic muscular dystrophy 1, or Steinert’s disease.

Myotonic dystrophy is a progressive degenerative disease that affects an estimated 130,000 people in US, EU and Japan. There is currently no approved treatment available to slow or stop disease progression.

The collaboration will focus on the development of novel small molecules capable of correcting the consequences of the splicing deficit caused by the myotonic dystrophy 1 gene mutation. Through this approach, some of the molecular alterations caused by the disease process may be corrected and the progression of disease may be curtailed. The enabling technology was developed by Dr. Pascal Chartrand, a principal investigator at University of Montreal, and licensed to AmorChem by Univalor, the University’s technology transfer group. Discovery will take place at AmorChem’s medicinal chemistry incubator, NuChem Therapeutics, and in Dr. Chartrand’s laboratory. Roche will provide scientific support and will contribute R&D funding together with AmorChem.

“By targeting the molecular consequences of the genetic mutation that causes myotonic dystrophy, we aim to slow down or stop the progression of this currently untreatable, chronic and slowly progressing musclewasting disease,” said Luca Santarelli, global head of neuroscience, ophthalmology and rare diseases at Roche Pharma Research and Early Development. “The partnership with AmorChem fits well into our discovery externalization strategy, which aims to leverage external scientific excellence and experienced entrepreneurs to complement our internal portfolio of innovative drug programs.”

“We are very pleased to be working together with Roche to pursue this project. Not only is it a testament to the value of our ongoing collaboration with Dr. Chartrand and his team, but it also highlights the contributions made by our affiliate, NuChem Therapeutics,” said Inès Holzbaur, general partner at AmorChem.

Under the terms of the agreement, Roche will have the option to acquire an exclusive, worldwide license at the end of the collaboration. AmorChem may earn up to $107 million in total, based on developmental and commercial milestones, and single-digit tiered royalties.

Cancer cells often display a lower pH compared to normal cells: the pH level inside cancer cells is higher than it is outside. “In living organisms, these small pH changes typically occur in tiny areas measuring only few hundred nanometers,” says senior author and professor, Chemistry Department of the University of Rome, Tor Vergata Francesco Ricci.

“Developing sensors or nanomachines that can measure pH changes at this scale should prove useful in the fields of in-vivo imaging, clinical diagnostics and drug-delivery.”

“DNA represents an ideal material to build sensors or nanomachines at the nanometer scale” adds co-senior author Alexis Vallée-Bélisle, a professor at the University of Montréal’s Department of Chemistry and Department of Biochemistry. “By taking advantage of a specific DNA sequences that form pH-sensitive triple helix, we have designed a versatile nanosensor that
can be programmed to fluoresce only at specific pH values.”

Fluorescence is the emission of radiation, including visible light, caused by an exchange of energy.

“This programming ability represents a key feature for clinical applications –we can design a specific sensor to send a fluorescent signal only when the pH reaches a specific value which is, for example, characteristic of a specific disease,” adds first author Andrea Idili.

In the future, this recently patented nanotechnology may also find applications in the development of novel drug-delivery platforms that release chemiotherapeutic drugs only in the vicinity of tumour cells.

The research was supported by the European Research Council and the Natural Sciences and Engineering Research Council of Canada.

The GRDI was first implemented in 1999 and is now in its sixth funding cycle. At the beginning of each funding phase, departments and agencies strategically review their research priorities and hold peer-reviewed competitions for the allocation of funds to new projects. The renewal of the GRDI funding for another five years is a measure of the scientific successes of the initiative to date, which range from the identification of tumour-specific antibodies for use in cancer treatment to genomics-based diagnosis of invasive and damaging species such as the fungus causing sudden oak death.

The Feds are committing $99.5 million to the initiative over the next five years to continue research in agriculture, environment, fisheries, forestry, and health. Genomics is the science that studies DNA sequences and the complex interactions of genes found in living organisms.

As part of the announcement, two projects that were launched in 2012 will receive two years of additional funding:

• The Quarantine and Invasive Species project aims at developing diagnostic tools based on DNA barcoding for the early detection, surveillance and management of hundreds of species, focusing on those that are of quarantine concern. (Project name: Protection of Canadian biodiversity and trade from the impacts of global change through improved ability to monitor invasive alien and quarantine species)

• The Food and Water Safety project aims at developing increased speed and reduced cost of genomics based methods for pathogen isolation, detection and characterization. It also intends to develop a federally integrated database to manage, store and provide access to genomic data and related information from food and waterborne pathogens, focusing on Escherichia coli and  Salmonella Enteritidis.

The GRDI coordinates eight federal science departments and agencies in the field of genomics research: the National Research
Council of Canada, Agriculture and Agri-Food Canada, Health Canada, Fisheries and Oceans, the Canada Food Inspection Agency, Environment Canada, Natural Resources Canada, and the Public Health Agency of Canada.

Dr. Poirier announced his findings as the annual Alzheimer’s Association International Conference was taking place in Copenhagen. This large-scale study identified naturally occurring genetic variants that provide protection against the common form of Alzheimer’s disease, with the goal of identifying specific biological processes amenable to pharmaceutical interventions.

“We found that specific genetic variants in a gene called HMG CoA reductase which normally regulates cholesterol production and mobilization in the brain can interfere with, and delay the onset of Alzheimer’s disease by nearly four years. This is an exciting breakthrough in a field where successes have been scarce these past few years” says Dr. Poirier, whose previous research led to the discovery that a genetic variant was formally associated with the common form of Alzheimer’s disease.

“These latest genetic results from Dr. Poirier’s team are an important step forward in the understanding of Alzheimer’s disease neurobiology, and also the use of genetics to identify an interesting new molecular target that is amenable to therapeutic development” added Brigitte Kieffer, scientific director of the research centre of the Douglas Mental Health University Institute.

Over the past two decades, research efforts around the globe have focused on identifying genetic and environmental factors responsible for causing or accelerating the progression of the common form of Alzheimer’s disease. However, little was known about possible protective genetic factors that can delay or even prevent the disease onset in humans. It is well documented that a subset of older individuals who happen to be carriers of predisposing genetic factors for the common form of Alzheimer’s manage to escape the disease and live long and productive lives without any memory problems until their 90’s.

“What began with the question ‘what makes a particular aggressive form of breast cancer cells keep growing?’ turned into 10 years of systematic research to identify the enzyme PLK4 as a promising therapeutic target and develop a small molecule inhibitor to block it,” says Dr. Mak, director of The Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre, University Health Network and an internationally acclaimed immunologist renowned for his 1984 cloning of the genes encoding the human T-cell receptor.

In the lab, Dr. Mak`s scientific team used an approach that combined functional RNAi analysis with gene expression analysis in breast cancer-derived cell lines and in human breast cancers replicated in mice. Using these multidimensional data sets for human breast cancer, PLK4 was identified as a candidate target among 10,000 other targets for the development of anticancer therapeutics.

“The research showed that the aggressive form of basal breast cancer cells may be dependent on PLK4 for survival and that depleting it induced cell death,” says Dr. Mak. “This finding led to the identification of CFI-400945, a selective and orally active inhibitor of PLK4, which was shown to have significant anti-tumour activity as a single agent in a variety of preclinical tumour models.”

Another key finding was observing the inhibitor effect on tumor models with a gene PTEN deficiency as a biomarker – of huge interest because PTEN, a tumour suppressor, is known to be defective in as many as half of all advanced solid tumour cancers.

“If clinical testing supports our hypothesis that PTEN is a predictive biomarker for CFI-40095, we will have another way to tailor personalized cancer medicine based on an individual’s genetics,” he says.

Although breast cancer was the initial focus and featured in the study that was published, the team has also conducted experiments with other types of solid tumours, with similar results. The next phase of research will involve testing in humans, which was approved last year by Health Canada and the U.S. Food and Drug Administration.

“It may take several more years to determine the benefit for patients,” says Dr. Mak, “but we are happy to be able to provide this opportunity for our patients. We remain optimistic that we may have found a novel way to treat cancer.”

The research was funded by The Princess Margaret Cancer Foundation, the Canadian Institutes of Health Research and Genome Canada.

Dr. Mak talks about his research

Two Simon Fraser University psychologists have made a brain-related discovery that could revolutionize doctors’ perception and treatment of attention-deficit disorders. The Journal of Neuroscience has just published a paper about the discovery by John McDonald, an associate professor of psychology and his doctoral student John Gaspar, who made the discovery during his master’s thesis research. The discovery opens up the possibility that environmental and/or genetic factors may hinder or suppress a specific brain activity that the researchers have identified as helping us prevent distraction.

“This is the first study to reveal how our brains rely on an active suppression mechanism to avoid being distracted by salient irrelevant information when we want to focus on a particular item or task,” said McDonald.

McDonald, a Canada Research chair in Cognitive Neuroscience, and other scientists first discovered the existence of the specific neural index of suppression in his lab in 2009. But, until now, little was known about how it helps us ignore visual distractions.

“This is an important discovery for neuroscientists and psychologists because most contemporary ideas of attention highlight brain processes that are involved in picking out relevant objects from the visual field. It’s like finding Waldo in a Where’s Waldo illustration,” says Gaspar. “Our results show clearly that this is only one part of the equation and that active suppression of the irrelevant objects is another important part.”

The psychologists say their discovery could help scientists and health care professionals better treat individuals with distraction-related attentional deficits. The researchers are now turning their attention to understanding how people deal with distraction. They’re looking at when and why people can’t suppress potentially distracting objects.

The National Research Council of Canada (NRC) has signed a collaborative agreement with the National Aeronautics and Space Administration (NASA) to study the atmospheric effects of emissions from jet engines burning alternative fuels. With this cooperative work, NRC will take part in NASA’s ACCESS II project, the alternative fuel effects on contrails and cruise emissions.

The ACCESS-II experiments have already commenced at NASA’s Armstrong Flight Research Center in Edwards, CA. Testing involved the deployment of NRC’s CT-133 aircraft to Palmdale, CA, to fly alongside aircrafts from NASA and the German Aerospace Center. The objective of the experiments is to obtain inflight airborne emission measurements and contrail characteristics from aircraft burning both conventional jet fuel and blended alternative fuels. The collaboration on ACCESSII will result in the collection of complementary and unique flight test data that will be shared and reported to the International Forum for Aviation Research.

This important research will aid in the qualification and ready acceptance of the use of biofuels in aviation and open the door to future collaborations on alternative fuels tests.

University of British Columbia researchers have genetically engineered trees that will be easier to break down to produce paper and biofuel, a breakthrough that will mean using fewer chemicals, less energy and creating fewer environmental pollutants.

“One of the largest impediments for the pulp and paper industry as well as the emerging biofuel industry is a polymer found in wood known as lignin,” says Shawn Mansfield, a professor of Wood Science at the University of British Columbia.

Lignin makes up a substantial portion of the cell wall of most plants and is a processing impediment for pulp, paper and biofuel. Currently the lignin must be removed, a process that requires significant chemicals and energy and causes undesirable waste. Researchers used genetic engineering to modify the lignin to make it easier to break down without adversely affecting the tree’s strength.

“We’re designing trees to be processed with less energy and fewer chemicals, and ultimately recovering more wood carbohydrate than is currently possible,” says Mansfield.

Researchers had previously tried to tackle this problem by reducing the quantity of lignin in trees by suppressing genes, which often resulted in trees that are stunted in growth or were susceptible to wind, snow, pests and pathogens.

“It is truly a unique achievement to design trees for deconstruction while maintaining their growth potential and strength.”

The study, a collaboration between researchers at the University of British Columbia, the University of Wisconsin-Madison, Michigan State University, is a collaboration funded by Great Lakes Bioenergy Research Center, was published in Science.

Dalhousie University’s Hydrology Research Group has launched the first Nova Scotia Watershed Atlas and geo-database. Created in collaboration with Nova Scotia Environment (NSE), the atlas provides the first high-level assessment of the health and stressors of watersheds in Nova Scotia.

The atlas and geo-database provide research on watersheds across the province, in an easy-to-understand package. It makes the information usable to government as a management tool, and the public as an education tool.

Many small coastal watersheds are currently facing high levels of stress, and require more detailed investigation. While these areas can often be overlooked in traditional inventories, much of Nova Scotia’s population lives in these areas. As such, the new atlas was created to highlight threats to water quality and supply in watersheds.

“We have developed a model that identifies the threats to our watersheds, and which watersheds have the most stresses,” explains Shannon Sterling, director of the Dalhousie Hydrology Group, Dalhousie University. “We examine stresses related to water quality, stream habitat, flow change, and surface erosion. The watersheds that pop up as being among the most stressed are those containing highly developed coastal communities, such as Cornwallis, Cunard watersheds around Wolfville, the Sackville watershed near Halifax, and the Sydney watershed, near Sydney.”

Nova Scotia is unique in that it’s composed of many smaller watersheds that flow directly into the ocean, as opposed to being dominated by large watersheds, as is the case in Alberta, New Brunswick, Saskatchewan, Manitoba and British Columbia.

It also means that high-level watershed planning is a priority in Nova Scotia.

High-level assessments are useful for evaluating threats posed by non-point-source stressors, such as urban runoff pollution, released over a wide area because their impacts are not easily monitored or detected.

“This project has benefited Nova Scotian’s by providing information on water quality and quantity for our watersheds, developing a model that can be used to determine watershed health, and providing a map atlas and spatial database that enables the sharing of this information with water resource managers, academics, and all Nova Scotian’s across the province,” said Kevin Garroway, lead scientist, Nova Scotia Environment, Government of Nova Scotia.

Another part of the Nova Scotia Watershed Assessment Program is the geo-database that assembles provincial scale watershed information.

The atlas uses the information from the geo-database to compare threatened watersheds with those where protective measures are in place. The watersheds with the highest threat and with the least amount of protective measures are highlighted as high priority for more detailed investigation.

The map atlas and spatial database culminates three and a half years of gathering, checking and analyzing spatial information on Nova Scotia’s watersheds.