Biomarker tests to diagnose and prognose acute exacerbations of chronic obstructive pulmonary disease

There are 2.6 million Canadians with Chronic Obstructive Pulmonary Disease (COPD), representing 17% of adults between 35 and 80 years of age. COPD is a disease characterized by progressive loss of lung function that leads to shortness of breath, poor quality of life, reduced productivity, emergency visits, hospitalizations and deaths. The World Health Organization estimates that COPD will be the 3rd leading cause of death worldwide by 2030, accounting for more than 7 million deaths/year and 11,000 deaths/year in Canada. Most of the deaths and suffering occur during ‘lung attacks’, when patients’ COPD flares-up, in response to a respiratory tract infection. Lung attacks cost the Canadian health care system nearly $3 billion each year in direct expenditures.

There are no tests that doctors can use to diagnose lung attacks and no tests that can guide doctors on how these lung attacks should be treated. In this project, we will develop lab tests to enable rapid and accurate diagnosis of lung attacks and to help doctors figure out who will have another lung attack in the near future, so pre-emptive therapies can be implemented to avoid future attacks. These tests will prevent hospitalizations and deaths from COPD and help patients to receive the right therapies at the most appropriate times.

Alongside this Innovation to Commercialization award, Dr. Sin has also received Mitacs Accelerate Internship funding for this project, expedited through a partnership between Health Research BC and Mitacs. 

Technology for image-based screening to enhance protein production

New medicines being developed to treat complex diseases, such as cancer, multiple sclerosis, and rheumatoid arthritis are increasingly becoming large and complex molecules, such as proteins. These molecules must be produced using cells grown in a laboratory or production facility. A key bottleneck in the development of such new medicines is producing sufficient quantities of these molecules for various stages of rigorous testing to ensure safety and efficacy. This project will develop a technology to generate better producer cells in order to increase their productivity. This capability will dramatically reduce the timelines required to develop protein-based medicines, resulting in more available and cost-effective medicines for patients.

A smart multifunctional wound dressing for continuous monitoring and treatment of chronic injuries

Wound management is a major global challenge and poses a significant financial burden to the healthcare system due to the rapid growth of chronic diseases such as diabetes, obesity, and aging population. The ability to detect pathogenic infections and release drug at the wound site is of the utmost importance to expedient patient care. We recently developed an advanced multifunctional dressing (GelDerm) capable of colorimetric measurement of bacterial infection and release of antibiotic agents at the wound site. We demonstrated the ability of GelDerm to detect bacterial infections using in vitro, ex vivo, and small animal tests with accuracies comparable to the commercially available systems.

Wireless interfaces to digital image capture hardware such as smartphones were used as a means for quantitation and enable the patient to record the wound condition at home and relay the information to the healthcare personnel for following treatment strategies. Additionally, we showed the ability of GelDerm to eradicate bacteria by the sustained release of antibiotics.

In this I2C application, we propose to support the commercialization of GelDerm through

  1. developing a multi-nozzle automated dispensing system as a scale-up manufacturing methodology for producing high volumes of GelDerm,
  2. developing a sterile packaging strategy for long-term storage of GelDerm and
  3. performing preclinical safety and performance studies in porcine model.
     

Novel nanomedicines for resolving inflammation as a treatment for type 2 diabetes

This project proposes a new nanomedicine approach to treat type 2 diabetes (T2D). Studies in humans and mice have shown that inflammation in fat tissues and the pancreas is a major driving force for the development of obesity-induced insulin resistance and diabetes. A major limitation of current drugs is that they distribute over the entire body, exposing all cell types, while only a small amount reaches the desired target cells at disease sites, such as macrophages in inflamed tissues. This results in limited drug efficacy and unwanted side-effects. We aim to develop a new treatment for T2D that exploits the natural physiological processes to suppress inflammation in macrophages within fat tissues and the pancreas with high potency. We will use lipid nanoparticles (LNP), which are drug delivery systems customized to stably carry a large amount of drugs to macrophages.

Scientific development in this project will involve testing of LNP containing immune-modulating drugs in obese, diabetic mice, and measuring the anti-inflammatory and anti-diabetic effects. With close to half a billion people worldwide suffering from T2D, we believe that the proposed cell-specific treatment can have a significant impact on health and the economy.

Developing a safe and effective analgesic for chronic pain relief

About 6 million Canadians report a form of chronic pain, yet half of the sufferers do not get enough pain relief from their medications. This severely affects their quality of life and has significant social and economic burdens. Opioid medications, such as morphine, are the most powerful pain killers available, but these drugs also cause serious side effects, such as suppressed breathing, leading to a high risk of death from overdose.

In 2016, there were 2,861 opioid overdose deaths in Canada, and British Columbia (BC) reported the highest opioid-related death rate, which was three times the national average. The overdose rate in BC increased 17-fold from 2011 to 2016. This worsening opioid epidemic resulted in changes in opioid prescribing standards, and half of the chronic pain sufferers can no longer access opioid drugs in BC. Dr. Li will lead a team to develop a new, effective, and safe drug for chronic pain relief. This new drug will improve pain relief options and access for patients who suffer from chronic pain.

The team will work with companies to ensure this new drug is readily available to pain sufferers through primary care to all populations in BC and the whole of Canada.

Improving cancer immunotherapy using G-CSF-blocking antibodies to overcome myeloid cell-mediated immunosuppression

Half of all Canadians will develop cancer and 1 in 4 will die of the disease. Cancer immunotherapy is a promising solution applicable to multiple types of cancer. The immune system plays a critical role in removing tumour cells. However, tumours escape the immune system to continue growing. Immunotherapy can enhance the immune system's ability to fight cancer and, in some cases, achieve long-lasting remission. However, many cancers do not respond to currently available immunotherapies.

In partnership with ME Therapeutics, we have developed antibodies targeting G-CSF, a protein overproduced by several major cancer types that induces immune suppression and may cause resistance to immunotherapy. Blocking G-CSF reduced the number of colon tumours and normalized immune system function in a mouse model of colon cancer.

We have selected a lead antibody that can successfully bind and inhibit G-CSF both in cell culture and mouse model systems. Our plan is to develop new animal models to test if blocking G-CSF can make resistant tumours sensitive to immunotherapy as well as to evaluate G-CSF in patient tumour tissue. Overcoming treatment resistance will substantially impact primary health care for cancer patients. 

Novel bioengineered probiotics increase colonization and persistence in the gut enhancing bioavailability and their therapeutic potential for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a major global health burden and the rapid surge in pediatric cases in Canada over the past decade is raising alarm bells. Current pharmaceutical therapies are risky or ineffective, cost and health-wise, especially for long-term use and are associated with severe side effects. Therefore, new alternative therapies for IBD are needed urgently. Probiotic therapy, which is the ingestion of non-pathogenic microorganisms to provide health benefits, is considered a potential treatment option. However, clinical trials using probiotics for IBD treatment have yielded very inconsistent and difficult to interpret data.

Specific to IBD, the gut environment is highly inflamed and oxidized; these properties may interfere with the growth and therefore beneficial effects of probiotics. As such, current probiotics are ineffective at persisting in the hostile gut of IBD patients. A novel therapeutic approach is to engineer designer probiotics that strategically target these limitations. The present invention relates to bioavailable and optimized genetically-engineered recombinant probiotic bacteria with enhanced therapeutic potential, for use in treating IBD.

Here we propose that our novel patented next generation microtechnology is an alternative to traditional probiotics to enhance bioavailability and is a potential alternative therapeutic option for IBD. This proposal aims to test how the designer probiotics enrich gut health in pre-clinical
models.

A GlycoCaged drug delivery system to improve the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is lifelong, debilitating condition that afflicts one in every 150 Canadians. Worryingly, the number of people diagnosed with IBD is rising worldwide, including among new Canadians and children. There is currently no cure for IBD, so treatment options are limited to managing symptoms with anti-inflammatory drugs.

Unfortunately, the oral administration of classical steroid IBD drugs is complicated by undesired side effects that result from premature uptake in the stomach and small intestine. Dr. Brumer and colleagues have recently developed a novel approach to link anti-inflammatory steroids to a complex carbohydrate from vegetables. This carbohydrate protects the steroids, allowing them to pass to the lower bowel, where they are released by beneficial bacteria of the microbiota.

Dr. Brumer and colleagues have validated this 'GlycoCage Technology' in the laboratory, including preliminary testing with human gut bacteria and in a preclinical animal model of IBD. The next steps in this research include further testing in additional animal models to determine dosage, safety, and efficacy. This will provide essential data before progressing to human trials and clinical application.

ACCEss-SCI: Adapting community centres to enhance exercise in spinal cord injury

Co-leads:

  • Tania Lam
    University of British Columbia
  • Ross MacDonald
    City of Surrey
  • Jaine Priest 
    City of Vancouver

Trainee:

  • Alison Williams
    University of British Columbia
  • Sharon Jang
    University of British Columbia

There is overwhelming evidence that regular physical activity is critical for reducing secondary health complications and improving quality of life for people with spinal cord injury (SCI). However, individuals with SCI face many barriers to exercising; the most common is accessing appropriate fitness facilities and fitness professionals with specialized knowledge in adaptive physical activity.

Since 2013, the Physical Activity Research Centre (PARC) at the International Collaboration on Repair Discoveries (ICORD) has provided adaptive physical activity opportunities to over 300 individuals with SCI. PARC previously created professional development workshops about physical activity for individuals with SCI. These workshops were conducted for UBC students, SCI peers, and local community fitness leaders; they were well received and there is interest for more continuing education programming. Research was also conducted to show the feasibility, acceptance, and health benefits of adaptive group exercises programs such as arm “spin” classes, circuit training, and boxercise. The goal is to extend these initiatives to local settings.

The City of Surrey Parks, Recreation, and Culture department (CoS) and the Vancouver Board of Parks and Recreation (VPB) share a common vision with PARC — to make physical activity opportunities across the Lower Mainland universal and accessible to all. Both VPB and CoS have identified multiple community centres to expand adaptive physical activity programming, but need support to train fitness staff to advance this programming. This Reach award will facilitate the translation of PARC-created adaptive fitness programs to VPB and CoS community centres. PARC will support this translation by providing on-site training to community fitness leaders, professional development workshops, staff in-services, and an adaptive physical activity mentorship program. The benefits of these translational initiatives will be measured by the success in changing attitudes about physical disability and perceived barriers to implementing adaptive programs among community programmers and fitness instructors, and successful implementation of inclusive and integrated fitness class programs in VPB and CoS community centers.

Cellular resolution OCT for clinical ophthalmology

Two of the leading causes of irreversible vision loss in developed countries are age-related macular degeneration (AMD) and diabetic retinopathy (DR). These diseases lead to the death of photoreceptors, the light-sensitive cells in the retina located at the back of the eye.

Treatments are currently available for “wet” AMD and DR, but there are currently no effective treatments for “dry” AMD. The key to preserving sight is early diagnosis, and monitoring the effects of the novel therapies in development.

The current technologies for non-invasive retinal imaging systems include flood illumination fundus photography, confocal scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). The resolution attainable with these techniques doesn’t permit visualization of the photoreceptor mosaic. The limiting factor to this ability is the eyes themselves—the cornea and lens that focus light onto the retina do not have microscopic abilities.

Dr. Sarunic has developed a novel instrument combining wavefront sensorless adaptive optics (SA) with OCT to correct ocular aberrations. This novel SAO OCT can achieve cellular resolution imaging of the retina, visualizing the individual photoreceptors that form a mosaic pattern on the retina (akin to looking at the pixels in a camera). This SAO OCT design is compact and clinically friendly, and with further investigation and commercialization, could lead to improved diagnosis and treatment for those with vision loss.