Projects Funded 2020

2020 ALS Canada Clinical Research Fellowship

How advanced brain imaging can help to support ALS clinical trial enrolment and evaluation

Bridging the Gap: MRI texture and its pathological correlates in ALS

$200,000 awarded to Dr. Collin Luk at the University of Alberta

Traditional magnetic resonance imaging (MRI) is an excellent, non-invasive tool for helping doctors diagnose and monitor the progression of diseases like brain cancer or multiple sclerosis, and researchers continue to explore ways it can prove successful in identifying and understanding ALS.

With this award, Dr. Collin Luk will seek to validate an advanced MRI technique, called texture analysis, with the goal it could one day be used as a biological marker, or “biomarker,” of the onset and progression of ALS. Using this technique, Dr. Luk can detect very subtle changes in a brain image that are not visible with a regular MRI scan.

In order to validate this method, Dr. Luk will analyze MRI scans from people living with ALS and compare those with scans of post-mortem brain tissue generously donated from people who had ALS. The brain tissue will also be examined for pathological changes to ensure that the MRI scans accurately reflect the changes happening in the brain on a cellular level. He will collaborate with the Canadian ALS Neuroimaging Consortium (CALSNIC) to validate his findings.

If this new method proves to be successful, a non-invasive MRI scan could help predict disease progression, making it possible for people living with ALS to enroll in clinical trials earlier. It could also give researchers the tools they need to better evaluate the effectiveness of promising new treatments.

While completing this fellowship work, Dr. Luk will also be actively trained to provide care for people living with ALS as a neurologist at the University of Alberta clinic in Edmonton. Combining this cutting-edge clinical research work with a first-hand experience as a care provider will undoubtedly make Dr. Luk an asset in the drive towards a better understanding of the disease and achieving better treatment options.

2020 Mitsubishi Tanabe Pharma Canada Fellowship

 How wearable sensors could help to improve ALS clinical trials

Prediction of change in ALS disease state by tracking movement with wearable sensors

$200,000, awarded by ALS Canada in partnership with Mitsubishi Tanabe Pharma Canada (MTP-CA), awarded Dr. Gordon Jewett at the University of Calgary

ALS progression is typically self-reported and evaluated only during clinic visits, which can occur months apart. This approach offers only a single snapshot of the person’s performance and is susceptible to daily fluctuations in personal factors such as stress, sleep, diet, and fatigue, which can influence the outcome. As such, tools that can continuously evaluate motor function are needed.

Wearable sensors are becoming common practice in helping people track their personal health and there have been a number of studies in recent years that have begun to evaluate their applicability to ALS. These devices usually include an accelerometer and gyroscope which can monitor a person’s movement during normal daily activities), and can connect to a computer via Wi-Fi. Thus, by placing one of these sensors on an arm or leg, researchers can capture and relay difficulties with limb movement due to ALS.

With this award, Dr. Gordon Jewett will utilize his undergraduate background in biomedical software engineering to monitor limb movement in people living with ALS using a wearable sensor and utilize machine learning techniques to develop an algorithm that can predict functional decline. The study will also utilize the Canadian Neuromuscular Disease Registry (CNDR) as a means of recruitment and comparison of wearable data with standard clinical data. Collaboration with the Canadian ALS Neuroimaging Consortium (CALSNIC), which is also supported by the ALS Canada Research Program, will help to validate his findings and provide an additional layer to his work by determining if the changes observed in MRI brain scans correlate with functional changes measured by the sensors.

The ability to accurately measure the functional status of someone living with ALS from data collected through a wearable sensor could significantly benefit the design of clinical trials. This approach could be implemented as a precise, reproducible, convenient and cost-effective outcome measure in ALS clinical trials. It would also make participation more convenient with fewer clinic visits required.

Dr. Jewett will accompany this work with additional training as a neurologist at the University of Calgary ALS clinic. The unique expertise he brings to the field, combined with his clinical duties will be a very valuable addition to the Canadian clinical and clinical research landscape.

2020 La Fondation Vincent Bourque-ALS Canada Career Transition Award

A new biological target that could represent promising new antibody treatment strategy for ALS

Extracellular PPIA: a new target for an antibody-based therapeutic approach for ALS

$250,000 awarded by ALS Canada in partnership with La Fondation Vincent Bourque to Dr. Silvia Pozzi at the CERVO Brain Research Centre, Université Laval

In recent years, scientists have observed higher levels of a specific protein, called Peptidyl-Prolyl Isomerase A (PPIA), in the fluid that surrounds the brain and spinal cord in ALS mice. This has also been observed in people living with the sporadic form of the disease (i.e. those who have no family history).

PPIA is a protein that is typically found inside cells where it completes its normal function, however, when the protein is released into the fluid outside of cells (in this case referred to as extracellular PPIA or ePPIA) there can be a negative effect. Outside of cells, ePPIA can bind to another protein, called EMMPRIN, and this interaction is thought to activate a biological pathway that eventually contributes to motor neuron death.

With this award, Dr. Silvia Pozzi will explore a new therapeutic strategy for ALS that targets this toxic protein interaction. In this study, Dr. Pozzi will further explore the effects of the interaction between ePPIA and EMMPRIN on motor neurons as well as other support cells in the brain, such as glia cells, which are thought to also play a role in the onset and progression of ALS.

In order to block the interaction between ePPIA and EMMPRIN, Dr. Pozzi will develop an antibody that specifically targets EMMPRIN. Antibodies are proteins produced by the immune system to protect the body against foreign invaders like bacteria and viruses, and work by binding to specific proteins on harmful agents and triggering their removal and/or destruction.

By designing an antibody specific for EMMPRIN, Dr. Pozzi hopes to prevent the protein interaction thought to lead to motor neuron death. The ability of the antibody to reduce inflammation and motor neuron death will then be assessed in various ALS mouse models. If the antibody proves to be successful at preventing motor neuron death in mice, the next step will be to determine if similar effects can be seen in humans.

Dr. Pozzi hopes to use this project as a start to a career based on developing antibody-based treatments in the lab that can be elevated to human clinical trials and strengthen Canada’s leadership towards a future without ALS.