In February, RHI announced two new funding opportunities Preclinical SCI Research Towards Cures (PSRTC) and Emerging Interventions & Innovative Technologies (EIIT). These competitions were developed to meet the objectives of RHI's 2013 – 2018 Business Plan, to align with the areas of focus of the Cure, Care and Commercialization Programs and ultimately, help RHI move closer towards achieving its vision of a world without paralysis after spinal cord injury. RHI is pleased to announce the results of both funding competitions.
Proposals submitted underwent a thorough review process to ensure alignment to RHI’s goals, relevancy and scientific merit. The Review Committees included people with SCI and external subject matter experts. A key requirement for the applicants was to demonstrate 1:1 co-funding for the proposed projects.
Five projects from PSRTC and six projects from the EIIT were selected for funding after undergoing the review process. Each successful project has been awarded $100,000 CDN from RHI.
“The projects selected for funding are great additions to RHI’s portfolio of projects and programs aimed at bridging the translational “valleys of death” in the SCI research continuum. Among the projects selected for funding, there is a great mix of promising preclinical and clinical therapies, tools to improve the SCI research and development process, innovative technologies, and consumer-centric mobile health innovations. I am thrilled to see international collaborations, as well as collaborations with industry partners, among the successful projects. These collaborations represent new partnerships for RHI and are critical to moving closer to a world without paralysis after SCI,” said Bill Barrable, CEO of RHI.
Congratulations to the funding recipients and best of luck in pursuing these exciting projects.
Continue reading to view summaries of the successful projects.
Preclinical Research Towards Cures
| Project Title: Evaluating SOX9 inhibitors in spinal cord injury |
| Principal Investigator: Arthur Brown, PhD |
Lead Organization: University of Western Ontario |
| We have identified a protein, SOX9, as an ideal target for spinal cord injury therapies as it negatively impacts on the ability of nerves to grow and form new connections. We have demonstrated that genetic SOX9 ablation improves recovery in a mouse model of SCI, suggesting that compounds that reduce SOX9 activity may be therapeutic in SCI. Using a cell culture system we have identified several compounds that inhibit SOX9 activity. The present application seeks support to test these compounds in animals with SCI. We have already protected the IP surrounding SOX9 inhibitors for the treatment of SCI. While we have initial commercial success with this technology the next phase of commercialization and clinical realization of this technology will require the demonstration that one or more of the identified SOX9 inhibitors improves neurological recovery in an animal model of SCI. |
| Project Title: Translational Development of Human Repulsive Guidance Molecule (RGMa) Neutralizing Antibodies for Neuroprotection and Regeneration in Spinal Cord Injury |
| Principal Investigator: Charles Tator, PhD, MD |
Lead Organization: University Health Network |
| Spinal cord injury (SCI) is a devastating condition occurring in approximately 1800 Canadians annually. Currently, this is no effective treatment for major SCI. The neuropathological effects of SCI are often progressive, resulting primarily from neuronal and glial cell death and damage to the nerve fibres (axons) that transmit messages along the spinal cord. Axonal regeneration in the mature central nervous system (CNS) is minimal and CNS neurons are particularly susceptible to apoptotic cell death when injured. We propose a therapeutically relevant strategy for SCI using human antibodies developed by our industrial partner, which neutralize the inhibitory Repulsive Guidance Molecule (GRMa) and the functionality of its receptor. This approach limits neuronal and axonal degeneration and also promotes axonal regeneration after SCI. These human RGMa antibodies are ready for clinical application to SCI and this proposal is the next step towards their translational development for SCI therapy. |
| Project Title: Therapeutic potential of human induced pluripotent stem-cell derived neural precursor cells in cervical spinal cord injury |
| Principal Investigator: Michael Fehlings, MD, PhD |
Lead Organization: University Health Network
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| Over half of traumatic spinal cord injuries (SCIs) occur in the cervical (neck) region, resulting in severe neurologic deficits including loss of upper limb function. Despite the great need, there are currently no therapies that provide meaningful functional recovery. There is compelling preclinical data to support the use of cell-based therapies in traumatic SCI, however there is little known about the capacity of humans cells to generate recovery. We will address these key knowledge gaps by using a clinically relevant model of contusive-compressive cervical injury to test the mechanisms and efficacy of neural precursor cells (NPCs) derived from human pluripotent stem cells (hiPSC) at promoting repair and functional improvement. This work represents a mechanistic focused extension to our recently awarded grant and will prove a great advancement toward bringing a novel cell-based therapy closer to clinical translation. |
| Project Title: MicroRNA Biomarkers for Acute Spinal Cord Injury |
| Principal Investigator: Brian Kwon, MD, PhD |
Lead Organization: University of British Columbia |
| Therapeutic development for spinal cord injury (SCI) is severely hindered by the difficulty in conducting clinical trials, which to date have relied solely on functional outcome measures for patient enrollment, stratification, and evaluation. Such outcome measures are often impossible to perform in the early trauma setting thereby excluding otherwise eligible patients from the trial. Biological biomarkers that accurately classify severity and predict neurological outcome can offer a paradigm shift in the way SCI clinical trials are conducted. In this preclinical study we will examine the profiles of microRNA (miRNA) in blood and cerebrospinal fluid (CSF) in a large animal model of SCI, to determine their utility as biomarkers in SCI. As trauma to the spinal cord is most directly reflected in the surrounding CSF, a comparison between miRNA levels in both blood and CSF is particularly valuable from a translational perspective to interpret which changes within blood are due specifically to the SCI. |
| Project Title: Preclinical Modeling of SCI - A China-Canada Collaboration |
| Principal Investigator: Wolfram Tetzlaff, MD, PhD |
Lead Organization: University of British Columbia |
| In our surveys of over 325 scientific and clinical SCI researchers and over 220 individuals with SCI, the majority felt that invasive and potentially risky treatments such as stem cell transplants should be tested for safety and efficacy in large animal and primate models prior to human trials. We have ample experience with rodent and large (pig) mammalian SCI models and we now seek to complete the continuum of preclinical modeling by establishing a non-human primate model of SCI. However, this is not feasible in Canada. We therefore collaborate with Dr. Qingan Zhu, a UBC trained bioengineer, now professor at the Southern Medical University, Guangzhou and the AAALAC accredited primate centre Landau. This joint venture will bring tremendous synergies between Canada and China in the development of an invaluable and accessible model for evaluating novel and potentially risky SCI therapy candidates in the final stage prior to translation. |
Emerging Innovations & Innovative Technologies
| Project Title: Continuous Positive Airway Pressure (CPAP) Treatment for Obstructive Sleep Apnoea after Acute Quadriplegia Study (COSAQ) |
| Principal Investigator: Najib Ayas, MD, MPH |
Lead Organization: University of British Columbia |
| We seek funding to support the Vancouver site (GF Strong) to complete the landmark Auto-titrating Continuous Positive Airway Pressure Treatment (CPAP) for Obstructive Sleep Apnoea (OSA) after Acute Quadripleiga (COSAQ) study. COSAQ is an Australian-led, international investigator-initiated, collaborative, parallel, randomized controlled trial designed to determine if nocturnal CPAP treatment for OSA will improve neurocognitive function in acute quadriplegia. The evidence from COSAQ could result in fundamental change in acute respiratory management and functional outcomes in quadriplegia. The specific aim is to determine whether nocturnal CPAP treatment improves neuropsychological function, quality of life and breathing in acute quadriplegia and OSA. It will determine if the “benefit is worth the burden”; whether wearing a CPAP mask overnight when you have limited or no hand function is worth it in terms of being able to concentrate better, to improve rehabilitation, to learn and to regain independence. |
| Project Title: The SENSIMAT for Wheelchairs |
| Principal Investigator: David Mravyan, P.Eng, MBA |
Lead Organization: Sensimat Systems Inc. |
| RHI has identified pressure ulcers as an important issue under the “RHI Care Program”. The devastation of pressure ulcers is well documented in wheelchair users and not only causes a great deal of patient pain and suffering, but is associated with a financial burden of $14 Billion USD/year to the North American healthcare system. Sensimat Systems has created an innovation that can potentially prevent pressure ulcers: The SENSIMAT. The SENSIMAT is a thin, wireless mat of pressure sensors inserted underneath a wheelchair cushion, connects via Bluetooth to the SENSIMAT mobile app, and allows 24/7 monitoring of wheelchair users. Through the SENSIMAT web portal, healthcare professionals can monitor their patients, gain insights into sitting behaviour and provide better care. Sensimat Systems has proposed a study to test the effectiveness of the SENSIMAT in a real-world setting that will revolutionize the way we think about pressure ulcer prevention. |
| Project Title: Granzyme B Inhibition to Accelerate Pressure Ulcer Wound Closure and Reduce Recurrence |
| Principal Investigator: David Granville, PhD |
Lead Organization: University of British Columbia |
| Pressure ulcers (PUs) in spinal cord injury (SCI) patients are frustrating to deal with for all involved and since they are very slow to heal they impact on health care budgets and policies. The normal wound healing process involves cleavage of skin proteins. However excessive cleavage of necessary proteins can impair the wound healing process. Granzyme B (GzmB) is an enzyme which may contribute to excessive cleavage of proteins required for wound healing. Preliminary data show that GzmB levels are increased in PU wound fluid and inhibition of GzmB accelerates wound healing models in chronic wounds. In this project, inhibitors of GzmB activity will be tested for their ability to accelerate PU wound healing and to help prevent recurrences. The goal of this project is to take a GzmB inhibitor through key stages of research that would allow development of a novel therapy for SCI patients with PUs. |
| Project Title: Pilot of a mobile platform to inform, support, and engage people with acute spinal cord injury and their health allies in rehabilitation and community integration |
| Principal Investigator: Ben Mortenson, PhD |
Lead Organization: University of British Columbia |
| An informed and engaged patient and family may have better outcomes in sub-acute spinal cord injury (SCI), but SCI education is difficult during a compressed and emotionally exhausting hospital stay. The coordination of care service for SCI is complex given the large number of providers involved. Patient Storylines is a mobile platform that is designed to 1) empower the patient through bite-sized information provided daily, 2) engage and motivate the patient through patient, provider, peer, and informal and formal caregiver (“health allies”) generated health requests, and 3) improve communication and coordination by connecting health allies (the “circle of care”) in a networked messaging system. The Patient Storylines intervention is intended to increase engagement in the rehabilitation process and improve adherence to rehabilitation plans. The purpose of this project is to refine the platform for use in people with SCI and to explore the feasibility of using it in practice and as part of a larger multi-site experimental trial. |
| Project Title: Urodynamic and Clinical Efficacy of Mirabegron among Neurogenic Bladder Patients |
| Principal Investigator: Blayne Welk, MD; Karen Ethans, MD |
Lead Organization: University of Western Ontario; University of Manitoba |
| People with spinal cord injury (SCI) often suffer from neurogenic bladder dysfunction, causing symptoms of urinary urgency, increased urinary frequency and urinary incontinence, which can significantly reduce their quality of life. This is commonly treated with anticholinergic medication, which is associated with undesirable side effects including dry mouth, cognitive changes, and constipation. Mirabegron is a new medication for overactive bladder that causes bladder relaxation, which reduces negative bladder symptoms with minimal side effects. This multi-centre, randomized, placebo controlled 10-week clinical trial with 144 subjects will be the first to assess mirabegron for the treatment of neurogenic bladder dysfunction. This area of study is one of RHI’s top priorities, and is one of the areas of high importance for people with SCI. With this clinically relevant research, results can be immediately translated into improving patient care. |
| Project Title: Effects of powered exoskeletal and conventional physiotherapy locomotor training programs on walking ability in individuals with an incomplete spinal cord injury: A crossover study |
| Principal Investigator: Dany Gagnon, PhD, PT |
Lead Organization: Université de Montréal |
| The use of trunk and lower limb powered exoskeleton devices in walking ability training among individuals with an incomplete spinal cord injury (iSCI) represents an emerging therapeutic alternative to rehabilitation. Surprisingly, few studies have investigated the use of powered exoskeleton devices and limited evidence is available. Eighteen adults with an iSCI will be randomized to complete either a powered exoskeletal with the EXOLEGS™ or a conventional locomotor training program. Upon completion of the first program, and after a one-week between-program break, participants will complete the second program. Each locomotor training program will offer three 60-minute treatments per week for four weeks. Baseline, between-program, final and 1-month follow-up clinical and laboratory assessments will confirm the effects of the locomotor training program with a powered exoskeleton and level of satisfaction with the assistive technology. Assessments will also determine whether powered exoskeletal locomotor training results in greater immediate and short-term gains than conventional therapy. |