Projects Funded 2021

Table of Contents

2021 ALS Canada-Brain Canada Discovery Grant Program

Can image-guided focused ultrasound technology aid in the delivery of promising new ALS therapies?

Gold and BBB opening in ALS (the GOALS trial): A phase 2a, open-label, single-arm clinical trial of oral CNM-Au8 coupled with primary motor cortex blood-brain barrier opening using transcranial MR-guided focused ultrasound in amyotrophic lateral sclerosis

$125,000 awarded to Dr. Agessandro Abrahao, Sunnybrook Health Sciences Centre, in collaboration with Dr. Lorne Zinman, Dr. Nir Lipsman, Sunnybrook Health Sciences Centre, Dr. Kullervo Hynynen, Dr. Simon Graham, Dr. Jamie Near, Sunnybrook Research Institute, Dr. Sanjay Kalra, Dr. Kelvin Jones, University of Alberta, Dr. Isabelle Aubert, and Dr. Sonam Dubey, Sunnybrook Research Institute

CNM-Au8, developed by Clene Nanomedicine Inc., is an oral liquid suspension of gold nanocrystals that is being investigated as a possible treatment for ALS. In preclinical ALS models in the lab, CNM-Au8 was shown to improve motor neuron function and survival by increasing energy production within cells and lowering oxidative stress. The efficacy of CNM-Au8 as a potential treatment for ALS was previously studied in a Phase 2 clinical trial, called RESCUE-ALS. Although topline results revealed the trial did not meet its primary and secondary endpoints, the company indicated they were pleased with the results which show a potential for efficacy and as such feel it is important to confirm the results in a larger trial. CNM-Au8 is also currently being tested in the HEALEY ALS Platform Trial with topline results expected in the second half of 2022.

With this grant, Dr. Abrahao and his team propose to conduct a Phase 2a clinical trial investigating CNM-Au8 coupled together with a technique called MR-guided focused ultrasound (MRgFUS). Previously supported with a 2017 ALS Canada Project Grant, the team has shown that MRgFUS can safely and temporarily enhance permeability of the blood-brain barrier (BBB), a specialized barrier that protects the brain from substances in the bloodstream including some drugs. Researchers are hopeful that delivering CNM-Au8 alongside MRgFUS will allow for more of the investigational drug to reach affected motor neurons in the brain.

This study will be the first to investigate MRgFUS in conjunction with an experimental ALS therapy. The clinical trial, which aims to recruit 10 volunteers with ALS, will be open label meaning every participant enrolled will receive the active treatment for up to 8 weeks. Participants will be followed to assess the safety and feasibility of the proposed treatment, as well as to measure whether there is enhanced delivery of CNM-Au8 to the brain and how the body breaks down the drug internally. This proof-of-concept study is a promising next step in developing a non-invasive way to deliver ALS therapeutics to the brain.

Can a cutting-edge imaging technique identify a link between a signalling pathway in the brain and ALS?

Quantitative PET/MR imaging of brain derived neurotrophic factor (BDNF) / tropomyosin related kinase B (TRKB) signaling in ALS – decoding a potential pathogenetic pathway

$125,000 awarded to Dr. Freimut Juengling, in collaboration with Dr. Sanjay Kalra and Dr. Ralf Schirrmacher, University of Alberta

A well-known neuroprotective substance, called brain derived neurotrophic factor (BDNF), is activated in the brain by a receptor called tropomyosin related kinase B (TrkB). Studies have shown that disturbances in the BDNF/TrkB pathway can be present in some neurodegenerative diseases, including ALS. However, previous efforts of targeting and increasing BDNF production as a way to protect dying motor neurons in ALS have been unsuccessful. In fact, emerging evidence suggests that increasing this pathway may actually make motor neurons more vulnerable to damage and injury, by overstimulating them (a process referred to as hyperexcitability).

With this grant, Dr. Juengling and his team seek to better understand how the BDNF/TrkB pathway may impact motor neuron vulnerability and survival. Researchers will measure changes in BDNF/TrkB signalling in 30 people living with ALS, all at different stages of the disease. For this, they will use a sophisticated imaging technique that combines PET (positron emission tomography) with MRI (magnetic resonance imaging), which allows researchers to map changes within the brain as the disease progresses.

The results gained from this study will provide the research community with a better understanding of the role of BDNF/TrkB signalling in ALS and help to answer the question of whether this pathway should be boosted or supressed when exploring new therapeutic avenues for treating the disease.

Can novel biomarkers help researchers to evaluate the effectiveness of promising new ALS therapies?

Novel biomarkers of SOD1 pathology in familial and sporadic ALS

$125,000 awarded to Dr. Gerhard Multhaup, McGill University, in collaboration with Dr. Angela Genge, The Neuro (Montreal Neurological Institute-Hospital) at McGill University

Approximately 20 percent of inherited cases of ALS result from mutations in the SOD1 gene. It is thought that mutations cause the SOD1 protein to fold into the wrong 3D shape, a process referred to as misfolding, and gain a toxic function within motor neurons.

Originally, this accumulation of misfolded SOD1 protein was thought to only be found in individuals who carry SOD1 mutations, but recent studies have shown that SOD1 mutations may be present in a small percentage of sporadic cases as well (e.g., those without a family history of disease). Therefore, Dr. Multhaup and his team emphasize the importance of promoting the breakdown of these misfolded SOD1 proteins as a therapeutic strategy for all forms of ALS where SOD1 dysfunction is present.

In this study, the research team aims to develop biomarkers that can detect misfolded SOD1 protein in people living with ALS. Biomarkers are biological measures that can be used to understand the real-time processes happening in the body. By discovering new biomarkers to determine the levels of misfolded SOD1, researchers can better understand the effectiveness of drugs that work on clearing these toxic proteins.

An example of an investigational drug that aims to decrease the levels of misfolded SOD1 is AP-101, which is currently being studied in a global Phase 2 clinical trial. The work proposed by Dr. Multhaup and his team could help researchers to monitor the effectiveness of SOD1-targeted therapies, such as AP-101, and ultimately, help us better understand ALS disease processes.

Does hypermetabolism contribute to ALS disease processes?

Determination of hypothalamic neuropathology and metabolic defects in ALS

$125,000 awarded to Dr. Jeehye Park, in collaboration with Dr. Hoon-Ki Sung, The Hospital for Sick Children

Previous studies have indicated that increased metabolism (called hypermetabolism) is a common feature of ALS and can be associated with weight loss, which is often related to a poorer prognosis. The hypothalamus is the area of the brain responsible for regulating the body’s metabolism, and recent clinical studies suggest that this area may be compromised in people living with ALS.

Although these recent findings shed a light on a potential link between hypermetabolism and ALS, it remains unknown whether hypermetabolism actually contributes to the rate of disease progression. Moreover, little is known regarding how exactly the hypothalamus is damaged in ALS and whether this has a direct association with the disease.

With this grant, Dr. Park and her team aim to investigate these questions using a mouse model of ALS that carries mutations in the MATR3 gene. Dr. Park was previously awarded a 2016 ALS Canada-Brain Canada Career Transition Award and a 2019 ALS Canada Project Grant to develop and validate this mouse model and showed that these mice not only mimic the neurodegeneration seen in ALS, but also display signs of defects in the hypothalamus and an inability to gain weight.

By gaining a better understanding of the link between hypermetabolism and weight loss in ALS, and the biological pathways underlying hypothalamic dysfunction, these scientists should be able to pinpoint new targets and strategies for the treatment of ALS.

How could the loss of the normal function of C9ORF72 contribute to ALS?

Effects of C9ORF72 deficiency on inducing neuronal hyperexcitability in vivo

$125,000 awarded to Dr. Janice Robertson, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, in collaboration with Dr. Liang Zhang, University Health Network

Mutations in the C9ORF72 gene are the most common genetic cause of ALS. These mutations are unique in that unlike most other ALS-linked genes, where there is often a mistake in a single piece of DNA, C9ORF72 mutations involve a section of DNA that is abnormally repeated hundreds or even thousands of times. These repeat mutations result in less of the normal C9ORF72 protein being produced within cells, which may contribute to the disease process. Since this discovery researchers have sought to determine the biological function of C9ORF72 in order to better understand how loss of this protein can contribute to disease.

Dr. Robertson and her team have previously used a powerful technique called single-nucleus RNA-sequencing (snRNA-seq) to investigate the biological pathways the C9ORF72 protein may affect. In conjunction with additional studies in the lab, data showed that loss of C9ORF72 is associated with the upregulation of another receptor protein, called GluA1. This means that when C9ORF72 levels are reduced, the GluA1 receptor works overtime which can lead to activation of a cell death pathway called glutamate excitotoxicity, which is believed to be one of the targets for riluzole, the first approved therapy for ALS.

In this study, Dr. Robertson and her team propose to establish the relevance of these findings by investigating C9ORF72 deficiency and its effects on a mouse model of ALS. This project will provide a better understanding of how the loss of C9ORF72 can influence glutamate excitotoxicity in ALS, and potentially lead the way to identifying new treatment targets for the disease.

Can small tags on TDP-43 influence its abnormal behaviour in ALS?

Exploring the involvement of TDP-43 SUMOylation in ALS pathogenesis

$125,000 awarded to Dr. Maxime Rousseaux, University of Ottawa, in collaboration with Dr. Martin Duennwald, Western University

TDP-43 is a protein that is normally found inside the nucleus of a cell. However, in over 97 per cent of people with ALS, TDP-43 becomes trapped outside the nucleus in the cytoplasm where it forms aggregates or clumps. Unlike many other ALS-linked genes, however, mutations in the TDP-43 gene are responsible for this dysfunction in only a small subset of cases, with the cause for most people living with ALS still unknown.

Tags called small ubiquitin-like modifiers (SUMOs) can change how proteins function and where they are located in a cell. When SUMOs attach to proteins, that process is called SUMOylation. Scientists have found SUMOs on TDP-43, but nobody knows yet how these tags might change the structure, location, or function of the protein.

With this award, Dr. Rousseaux and his team aim to investigate the link between TDP-43 and SUMOylation in ALS, using a new mouse model generated in their lab. The team will investigate how SUMOylation occurs in the cell, how blocking the SUMOylation of TDP-43 may alter its activity, and whether SUMOylation can influence ALS disease processes.

Understanding how TDP-43 dysfunction could be regulated through SUMOylation is of great interest as the outcomes from the study will impact almost all people living with ALS and could open up new avenues of exploration for developing treatments targeting TDP-43.

Does this newly discovered protein variant play an important role in ALS?

Investigating the neuronal function of a novel HNRNPA1 variant

$125,000 awarded to Dr. Christine Vande Velde, Centre de recherche du CHUM at Université de Montreal, in collaboration with Dr. Marlene Oeffinger, Institut de recherches cliniques de Montréal (IRCM)

An important hallmark in understanding ALS was the discovery of dysfunction in a protein called TDP-43. TDP-43 is normally found in the nucleus, the central part of the cell. Problems with its transportation and function, however, are often seen in the motor neurons of people living with ALS, with TDP-43 being misplaced to an area outside the cell nucleus called the cytoplasm.

Dr. Vande Velde and her team have previously shown that a reduction in the amount of TDP-43 in the nucleus causes the code of another ALS gene called HNRNPA1 to be abnormally read, leading to the production of an alternative form of the protein called hnRNP A1B. Through a 2018 ALS Canada Project Grant, Dr. Vande Velde was able to explore some basic functions of hnRNP A1B, but it’s full biological function, and relationship to ALS remain unknown.

Researchers hypothesize that the disturbance in the type of hnRNP A1 produced in cells can contribute to neurodegeneration. In this study, they seek to understand more about the normal function of hnRNP A1B in several cellular processes, and how this can be linked to ALS disease progression.

Ultimately, the results from this study will not only provide mechanistic insights into the ALS-linked hnRNP A1B protein variant but also lay groundwork for the investigation of other protein variants which will be valuable for therapeutic and biomarker development in ALS.

Can undiscovered protein interactions influence FUS dysfunction in ALS?

Identification of protein interactions that regulate FUS mislocalization and aggregation in ALS

$125,000 awarded to Dr. Ji-Young Youn, SickKids Research Institute, in collaboration with Dr. Hyun Kate Lee, University of Toronto

Mutations in a gene called FUS can lead to potentially toxic, abnormal aggregation (or clumping) of the FUS protein within motor neurons. These mutations are strongly linked to the development of ALS. The exact mechanisms, however, for how this complex aggregation occurs and how this impacts key functions within motor neurons remain poorly understood.

Normally, the FUS protein is found primarily in the nucleus, the central part of the cell where our DNA is stored. When FUS mutations are present, these proteins leak out from the nucleus and accumulate in the cytoplasm. Dr. Youn and her team hypothesize that this change in location of the FUS protein results in different protein interactions within the cell that influence its toxic aggregation, and ultimately motor neuron health.

In this study, the researchers will use a technique called BioID to verify which protein interactions are gained or lost when FUS is transported outside of the nucleus, and additionally, how age-related stress impacts these. This work will help us to better understand how FUS mutations or age-related stress drive ALS and help to identify novel treatment strategies. This work also provides a model to test the cellular interactions of other ALS-linked proteins, which will be an invaluable tool to learn more about the molecular pathways that contribute to disease.

Could a new biomarker in the eye help to advance ALS research and care?

Imaging a new ALS biomarker in the eye

 $125,000 awarded to Dr. Yeni Yucel, in collaboration with Dr. Neeru Gupta, Unity Health Toronto

Biomarkers are biological measures that can be used to capture changes in our bodies, and often help to identify and track abnormalities. As such, biomarkers are of extreme importance in the diagnosis and treatment of various conditions. Unfortunately, existing experimental biomarkers for ALS can often be expensive, invasive, or not easily accessible by clinicians and patients. Thus, there is an urgent need for accurate and accessible biomarkers within the field.

When a certain part of a neuron becomes damaged, called the axon, a bubble-like feature called an axonal spheroid can be formed. These spheroids are commonly found in motor neurons in the brains and spinal cords of people living with ALS. Dr. Yucel and his team believe that the eye may be an important window to view and monitor this axonal injury.

With this grant, Dr. Yucel proposes to develop a reliable method to detect retinal spheroids in people living with ALS. Using widely available clinical eye imaging devices and advanced machine learning techniques, the team aims to design and validate imaging models that would estimate ALS disease severity. If successful, this project will establish the safe, non-invasive, rapid and relatively inexpensive biomarker for ALS which could be used to support ALS diagnosis, monitoring, and assessment of drug response in both the clinic and clinical trials.

2021 ALS Canada Trainee Awards

Doctoral Award

Could a new 3D model of the neuromuscular junction help advance drug screening in ALS?

Towards building a screenable human three dimensional (3D) neuromuscular junction (NMJ) in vitro model of ALS

$75,000 awarded to Maria José Castellanos Montiel, a PhD student in Dr. Thomas Durcan’s lab at the Montreal Neurological Institute and Hospital, McGill University

The neuromuscular junction (NMJ) is the place where motor neurons, the nerve cells that control voluntary muscles, connect to muscle fibers. This junction allows for signals from the brain to pass to muscles in order to perform voluntary movement. Many researchers believe that one of the earliest events in ALS is the detachment of motor neurons from muscles at the NMJ. Thus, it is important to develop models in the laboratory to study the NMJ, to better understand how it may be impaired in ALS.

With this award, Maria proposes to create a 3D model of the NMJ using induced pluripotent stem cells (iPSCs). iPSCs have become an invaluable tool when studying neurodegenerative disease as these cells retain the genetic information of the patient who donated them and can be transformed into motor neurons, or any other cell type in the lab.

With iPSCs derived from patients who carry different ALS-linked mutations, Maria plans to create 3D NMJ models with different genetic backgrounds to investigate how the NMJ and muscle function may be affected. The ultimate goal of this project is to develop models that can used for drug screening in order to identify compounds that may have a positive effect on NMJ function and someday have the potential to be advanced into promising clinical trials.

Does cerebrospinal fluid play a role in the progression of sporadic ALS?

Role of TDP-43 and SOD1 proteins in pathogenesis transmitted by CSF of ALS patients

$75,000 awarded to Amélie Poulin-Brière, a PhD student co-supervised by Dr. Jean-Pierre Julien and Dr. Silvia Pozzi at Centre de recherche CERVO, Université Laval

Recent studies from Dr. Julien’s lab suggest that the cerebrospinal fluid (CSF) of sporadic ALS patients (e.g., those without a family history of disease) may contain toxic factors that promote the spread of the disease throughout the central nervous system. Researchers hypothesize that the toxic effects may be due to the presence of misfolded TDP-43 and SOD1 proteins within the CSF, which have the potential to spread toxicity from cell-to-cell through a chain reaction inducing protein misfolding in healthy cells.

Previous studies revealed that when CSF collected from sporadic ALS patients is introduced into the CSF of mice, it can trigger neurodegeneration and functional deficits that are hallmark of ALS. In this project, Amélie will co-infuse CSF from sporadic ALS patients with antibodies that specifically target TDP-43 to investigate if depletion of TDP-43 may have a protective effect and how this might occur. She will then use antibodies to remove all TDP-43 or SOD1 from the CSF samples prior to infusion and examine the effect on disease. If these mice show less disease features compared to those infused with CSF still containing TDP-43 and SOD1, it will further implicate these proteins as potential contributors to the spread of ALS and highlight them as key therapeutic targets.

The results gained from this work hope to provide more insight into the mechanisms that underly the progression of ALS and aim to reveal whether targeting TDP-43 and SOD1 proteins in the CSF represents a viable strategy to explore for the treatment of ALS.

How might reduced levels of C9ORF72 contribute to ALS disease processes?

Role of C9ORF72 in synaptic AMPAR trafficking

$75,000 awarded to Belay Gebregergis, a PhD student in Dr. Janice Robertson’s lab at TANZ CRND and LMP, University of Toronto

In 2011, scientists discovered that mutations in the C9ORF72 gene are the most common genetic cause of ALS. These mutations result in reduced levels of normal C9ORF72 protein within cells, while also promoting the formation of additional toxic substances. But exactly how these changes contribute to causing ALS is not fully known. To determine how reduced levels of C9ORF72 protein may cause disease, researchers must first understand its normal function in cells.

Previously, Dr. Robertson’s lab showed that decreased C9ORF72 levels in mice can lead to increased levels of another receptor protein, called GluA1. Other evidence suggests that C9ORF72 may play a role in the movement, or trafficking, of proteins within cells, such as GluA1. This abnormal biology and increased levels of GluA1 caused by reduced levels of C9ORF72 may ultimately make motor neurons more vulnerable to glutamate excitotoxicity, a cell death pathway thought to play a role in ALS.

With this award, Belay aims to study the consequences of increased GluA1 levels and determine how this may lead to glutamate excitotoxicity in mice that have C9ORF72 removed. He will also investigate the mechanisms underlying GluA1 trafficking in motor neurons from these mice, and the potential role of C9ORF72 in the process. This work will help researchers to better understand the link between C9ORF72 and GluA1 trafficking in cells, as well as the mechanisms that underly the observed excitotoxicity which could help to identify new therapeutic targets.

Postdoctoral Fellowship

Can artificial intelligence detect bulbar ALS in Canadian French speakers?

Artificial intelligence for the diagnosis and monitoring of bulbar ALS in Quebec French

$110,000 awarded to Dr. Liziane Bouvier, a postdoctoral fellow in Dr. Yana Yunusova’s lab at Sunnybrook Research Institute

Thirty per cent of people with ALS have bulbar-onset ALS. This means they experience voice and speech changes at disease onset due to a loss of motor neuron function in the corticobulbar area, the area of the brain that controls the muscles of the face, head and neck. Almost all other people living with ALS will face voice and speech difficulties at some point in the disease.

Previously, with support from a 2019 ALS Canada Project Grant awarded in partnership with Orangetheory Fitness Canada, Dr. Yunusova and team showed that artificial intelligence (AI) algorithms can be trained on voice recordings from ALS patients to detect bulbar abnormalities, in some cases even prior to the onset of any clinically detectable bulbar symptoms. Furthermore, these AI methods were able to accurately measure and predict the progression of speech difficulties in people living with ALS. Despite these advancements, however, the work has not yet been adapted to French speakers.

In this project, Dr. Bouvier will develop AI tools to identify bulbar and pre-bulbar ALS in French speaking patients. The study aims to pinpoint the acoustic characteristics associated with the disease and its progression, and to train and validate an AI model based on these predicted findings. This work is of high importance for French speakers in Canada, with the goal of improving standard of care and access to clinical trials.

Does TDP-43 mislocalization contribute to impaired stress granule formation in ALS?

Investigating the role of the TDP-43/G3BP1 axis in ALS for therapeutic strategies

$165,000 awarded to Dr. Hana Fakim, a postdoctoral fellow in Dr. Christine Vande Velde’s lab at CR-CHUM, Université de Montréal

TDP-43 is a protein that behaves abnormally in the motor neurons of 97 per cent of people with ALS. It is usually found in the nucleus, but in people with ALS, it becomes trapped outside in the cytoplasm where it forms aggregates. Previous work in the Vande Velde lab showed that the mislocalization of TDP-43 to the cytoplasm also results in decreased levels of another protein, called G3BP1.

G3BP1 is an essential protein for the formation of stress granules, which are protective structures that healthy cells make when they are exposed to environmental stress. Stress granules protect vulnerable RNA (molecules that translate genetic instructions and oversee protein production) from becoming damaged. Recent evidence suggests that disruption of proper stress granule biology may play a central role in ALS disease processes.

With this award, Dr. Fakim will study the critical role that abnormal TDP-43 is thought to play in the regulation of G3BP1. Using cell culture and patient samples, Dr. Fakim will investigate whether G3BP1 levels are altered in the brains of people living with ALS and explore the biological mechanisms responsible for these changes. Additionally, antisense oligonucleotide (ASO) technology will be used to determine whether restoring normal levels of G3BP1 in mice can enhance cell survival. This work has important therapeutic potential for the significant percentage of ALS cases where TDP-43 abnormalities are present.

2021 ALS Canada Clinical Research Fellowship

Could this promising new biomarker also be a target for future ALS therapies?

Stathmin-2 aberrant processing as a biomarker of TDP-43 dysfunction in familial and sporadic ALS

$200,000 awarded to Dr. Vincent Picher-Martel at Massachusetts General Hospital

Abnormalities in a protein called TDP-43 are present in approximately 97 per cent of all ALS cases. Normally, TDP-43 is found in the nucleus of a cell (a central compartment where our DNA is located); however, in people living with ALS it is often found in the cytoplasm (the area outside of the nucleus) where it tends to form clumps, or aggregate, and is no longer able to function properly.

Researchers have long sought after a biomarker that could detect this TDP-43 abnormality in ALS patients in real time. With this award, Dr. Vincent Picher-Martel will study a promising new biomarker that may be able to do just that, called stathmin-2. This protein is essential for axonal growth and the maintenance of neurons. Recently, it was shown that the mislocalization and aggregation of TDP-43 can lead to the development of abnormal stathmin-2 within cells.

Here, Dr. Picher-Martel will further explore the potential for stathmin-2 as a biomarker for ALS by studying the levels of abnormal stathmin-2 protein found in the cerebrospinal fluid (CSF), blood and post-mortem tissues of ALS patients and correlating it with the individual’s clinical data.

In addition, using motor neurons derived from patient stem cells, he will investigate the role of stathmin-2 in various types of ALS to determine whether stathmin-2 is abnormal in all forms of ALS and how it influences motor neuron health. Using an antisense oligonucleotide (ASO), Dr. Picher-Martel will also investigate whether normal production of stathmin-2 can be restored in cells and if so, have a positive impact on the health of motor neurons. If successful, this would suggest that in addition to its potential role as a biomarker, stathmin-2 may also represent a promising new treatment target for future ALS therapies.

Dr. Picher-Martel will accompany this work with additional training as a neurologist while completing a two-year fellowship at Massachusetts General Hospital in Boston. The program represents an exceptional opportunity for training in clinical trials, drug development, translational medicine, and allows for collaboration with experts in the field worldwide. After completing the fellowship, Dr. Picher-Martel plans to return to Canada where he will undoubtedly be an asset in the drive towards a better understanding of the disease and achieving better treatment outcomes.

2021 Mitsubishi Tanabe Pharma Canada Fellowship

Could a screening tool help to identify early psychological distress in ALS and guide appropriate management?

The impact of psychological distress in ALS

$130,000, awarded by ALS Canada in partnership with Mitsubishi Tanabe Pharma Canada (MTP-CA), to Dr. Andrea Parks at Sunnybrook Health Sciences Centre

For people living with ALS, quality of life is significantly impacted by emotional well-being, yet the management of physical symptoms often becomes the primary focus of care. Currently, little is known about the prevalence and characteristics of psychological distress in ALS and there is no standardized screening tool or management strategy in place to address this psychosocial issue.

With this award, Dr. Andrea Parks aims to characterize the different types of psychological distress observed in ALS patients and determine its predictors, with the long-term goal of developing and validating a routine screening tool to enhance early identification of psychological distress and guide appropriate management strategies.

Through this study, psychological distress will be measured in at least 100 people living with ALS using multiple online, self-administered instruments and a survey to explore various dimensions of psychological distress, including emotional, spiritual, existential, and financial distress. Demographic and clinical data will also be collected to investigate the relationship between demographic/clinical

characteristics and subtypes of distress. Finally, Dr. Parks will seek to validate whether a screening tool commonly used in the oncology field, called the Distress Thermometer, can accurately identify clinically significant distress in ALS patients.

The ability to identify, and subsequently manage, psychological distress will address a major unmet need for ALS patients and their families and ultimately improve quality of life. Additionally, investigating psychological distress in ALS, as proposed in this study, will provide key data to support the potential for programs and funding for mental health services for Canadians living with ALS.

While completing this fellowship, Dr. Parks will also be working towards a master’s degree in Quality Improvement and Clinical Epidemiology through the Institute of Health Policy, Management, and Evaluation at the University of Toronto. From early in her career, Dr. Parks has committed herself to the care of ALS patients and the unique expertise she brings to the field will help provide Canadians living with ALS the highest quality of care.