Itch, or chronic pruritus, is a common condition affecting about 40% of adults aged 65 and older. For many, chronic pruritus can significantly reduce quality of life. For these individuals, existing treatments like systemic or immunosuppressive drugs are often unsafe due to age-related health conditions. A protein called Granzyme B (GzmB), which is active in aging and inflamed skin, has been linked to itch severity, but its exact role in causing itch is still unknown.
This research aims to uncover how GzmB contributes to itch in aging skin. First, we will study the connection between GzmB levels and signs of itch in skin samples from elderly patients with eczema. Next, we will investigate how GzmB affects skin cells, nerves, and immune responses, focusing on pathways that worsen itch. Finally, we will test a promising new topical GzmB-blocking gel treatment, VTI-1002, in experimental models of itch.
By understanding how GzmB causes itch and testing potential treatments, this study could lead to safe, targeted therapies that improve the quality of life for older adults with chronic itch.
Research Location: International Collaboration on Repair Discoveries (ICORD)
Building Capacity for Research Partnerships: A Health Learning System Approach
People with SCI often struggle to find research that reflects their needs. One way to improve this is through research partnerships, where researchers and people with lived experience work together. However, many researchers do not have the training or support to build strong partnerships, and research institutions do not have systems in place to make engagement easier. This project will help change that by developing a long-term support system for research partnerships at ICORD. The first step is launching a training course to help researchers and trainees learn how to work meaningfully with partners. I will also work with ICORD’s Meaningful Engagement Committee to create ways for the institution to better track, support, and strengthen partnerships over time. Finally, I will connect with other SCI research institutions to see how this approach can be adapted beyond ICORD. This work will help make research partnerships more effective, ensuring SCI research is relevant, useful, and impactful for the people it is meant to serve.
Acute intermittent hypoxia as a treatment of diabetic-induced sensory neuropathy, wound healing deficits, and motor system decline
Knowledge gap: Diabetes is a leading cause of amputation because it causes nerve damage (numbness, pain), skin wounds (infections), muscle loss (weakness), and bone thinning (fractures, osteoporosis). Acute intermittent hypoxia (AIH, breathing cyclical low & normal oxygen levels x2 hours) promotes healing and treats other diseases of the nervous system. We believe AIH will improve the effects of diabetes on the nerves, skin, muscle, and bone of the leg.
Aim 1 (Rodent Model): we will investigate if AIH treats nerve, skin, muscle, and bone of the diabetic leg. Animals with diabetes treated with AIH will be compared to no-AIH controls using behaviour testing, specialized imaging, and assessment of tissue samples.
Aim 2 (Clinical): we will investigate if AIH improves recovery of sensation, decreases pain and improves wound healing for human patients with diabetes. Fifty patients will be recruited from the multidisciplinary lower limb reconstruction program for inclusion.
Expected Outcomes: Based on preliminary data, we believe AIH is a safe and effective strategy to treat the diabetic leg.
Impact: Without the need for surgery or medications, AIH may provide treatment for diabetic patients to treat pain, infection and amputation.
Sensorimotor interactions between the lower limb and pelvic floor: neuroplasticity and implications for management of urinary dysfunction after spinal cord injury
People with spinal cord injury (SCI) often experience problems with their bladder function, resulting in symptoms like urine leakage. The bladder and its associated structures are controlled by neural circuits located in the lower part of the spinal cord. This area also contains neural circuits that help control leg movements and sensation. Studies in animals showed that sensory input from the legs can affect muscles controlling urinary function. There is also evidence for such connections between these two systems in humans. For example, gait rehabilitation and electrical stimulation of nerves in the lower leg may help with bladder symptoms in people with neural injury. The reasons for these effects are unclear. However, our recent studies indicate that the pelvic floor muscles, which are crucial for maintaining continence, are activated when people with SCI walk with the help of an exoskeleton. To better understand these phenomena, this proposal will examine how sensory input from the leg affects pelvic floor muscle activity in able-bodied individuals and people with SCI, as well as the potential of using this neural connection to develop rehabilitation-based approaches to manage urinary dysfunction after SCI.
Improving motor prognosis after spinal cord injury
Spinal cord injury (SCI) leads to devastating muscle paralysis. My research has shown that paralysis is due, not only to interruption of communication across the damaged spinal cord, but also because of damage to the nerves and muscles outside the spinal cord, which are equally as important in producing strength. This unrecognized damage may influence prognosis and how a patient responds to treatment. Unfortunately, we do not routinely test the health of these nerves and muscles. This makes it very challenging for doctors to provide patients with accurate information about prognosis and also for patients to make proper decisions about treatment options. My project will showcase the health of nerves and muscles after SCI, using a combination of routine clinical and special laboratory techniques. This information will lead to:
- Identification of those at risk of nerve and muscle damage.
- Routine assessment of nerve/muscle health in clinical practice.
- The development of a tool to help patients make informed decisions about treatment.
The project will be conducted by my team at GF Strong Hospital and with collaborators in three other Canadian centres.
Transcutaneous spinal cord stimulation for treating neurogenic bladder dysfunction following spinal cord injury
As much as 80 percent of people with a spinal cord injury (SCI) develop urinary bladder problems. Recovery of bladder function is consistently rated as a top treatment priority for people with SCI. Left unmanaged, bladder dysfunction can result in frequent urine leakage or unwanted urine retention that often cause kidney or urinary tract infections which drastically reduce overall quality of life. Despite the prevalence of this issue, treatment for restoring bladder function remains under-emphasized in SCI research. Of even greater concern are consequences associated with rapid, and often life-threatening, increases in blood pressure triggered by bladder care. Electrical spinal cord stimulation via surgically implanted electrodes is a potential treatment option that has been shown to promote functional recovery after SCI by modulating silent spinal circuits. However, the surgical implantation of electrodes and the stimulator is invasive, expensive and has inherent risks. We propose to improve bladder function and prevent associated blood pressure surges via non-invasive spinal cord stimulation using electrodes placed over the skin, thereby minimizing patient risk and obviating the need for invasive and expensive surgery.
Multimodal characterization and classification of bio-signals to predict cardiac arrest
Sudden cardiac arrest (SCA), due to abrupt disruption of cardiac function, is a major health problem globally. SCA can happen to anyone at any age who may or may not have been diagnosed with heart disease. SCA has a poor survival rate of about 10 percent, with an estimated 35,000 deaths in Canada annually. With an increasing rate of cases (16 percent from 2017 to 2020), SCA remains a major public health issue in British Columbia. The most effective strategy to improve survival is to achieve rapid SCA recognition, given that for every minute without cardiopulmonary resuscitation (CPR) survival rates drop by 10 percent. Wearable devices may play a major role in decreasing SCA mortality, providing real-time cardiac information for early SCA detection. My aim is to develop a wearable SCA device with embedded sensors, and use their real-time physiological data combined with artificial intelligence algorithms, to make an accurate SCA detection system. This SCA detection system will be designed to identify SCA and alert Emergency Medical Services with the individual’s location (via GPS), enabling them to provide life-saving interventions in a timely manner.
Light and drug delivery coupled with biomaterials to improve motor function after spinal cord injury in animal models
Spinal cord injury (SCI) is a debilitating condition with no available cure directly affecting ~80,000 Canadians. The major challenges to overcome include: i) the limited spontaneous regeneration of nerve fibers (axons) after the injury; ii) scar tissue formation at the injury site (lesion), which inhibits the growth of axons; and iii) the difficulty in guiding axons to grow across the lesion. The present work proposes a novel solution that combines optical stimulation technology and biomaterials to promote axonal growth, inhibit the formation of scar tissue using targeted drug delivery, and guide growing axons across the lesion. My team has developed fully implantable multifunctional neural probes for the delivery of both light and drugs to the spinal cord injury site as well as biomaterials to guide the growth to axons across the lesion. The MSFHR Scholar Program would support our work to integrate these strategies and create a therapy that helps us understand the combined effects of light stimulation, drug delivery, and axon guidance on motor function recovery after SCI in animal models. The outcomes will support treatment development for SCI based on a better mechanistic understanding of regeneration.
Paediatric spinal cord injury in Canada: Using administrative claims data to examine long-term health outcomes and healthcare utilization
A spinal cord injury (SCI) is defined as damage to the spinal cord that results from traumatic (e.g. motor vehicle accidents or falls) or non-traumatic (e.g. spina bifida or tumour diagnosis) causes. Children with SCI often require extensive medical follow-up and rehabilitation, and are at increased risk of adverse health effects (such as bladder issues, respiratory and cardiovascular disorders, and death) compared to children without SCI. Despite presumed increases in the number of Canadian children living with SCI over time, little is actually known about paediatric SCI in Canada. Using electronic health data from British Columbia and Ontario and health analytics, my proposed research aims to address existing SCI knowledge gaps by 1) developing national case definitions for traumatic and non-traumatic paediatric SCI, 2) estimating the number of Canadian children living with SCI, and 3) increasing understanding of long-term health outcomes and healthcare utilization among children with SCI. Findings from this research will, for the first time, describe paediatric SCI in Canada, identify paediatric populations most at risk of SCI, and identify opportunities to improve paediatric SCI care in British Columbia and across Canada.
Non-invasive Neuroprosthesis for Cardiovascular Recovery Following Spinal Cord Injury
Spinal cord injury (SCI) not just causes paralysis but also more devastating issues such as impaired blood pressure (BP) and heart rate regulation, which are among the leading causes of illness and death among this population. The individuals with SCI above the mid-thoracic level commonly suffer from highly labile BP that rapidly reaches alarmingly high and low levels within the same day. These extreme BP fluctuations often result in seizures, ruptured brain blood vessels and even death. Hence it is not surprising that the individuals with SCI rank improving heart and blood vessel function among the highest priorities for recovery, even higher than regaining the ability to walk again.
The goal of this proposal is to test the potential of non-invasive spinal cord stimulation (delivered through skin) to promote blood pressure control in a rat model of SCI. Our laboratory's pilot experiments have already demonstrated that non-invasive stimulation is feasible and effective in humans with SCI. Present proposal will allow us to thoroughly understand the underlying mechanisms and enable widespread clinical use of spinal cord stimulation in improving quality of life of individuals with SCI.