Projects Funded 2023

Table of Contents

2023 ALS Canada-Brain Canada Clinical Research Fellowship

Can we better understand the experience of younger middle-aged adults with ALS to help guide age-appropriate management of the disease?

Younger middle-aged adults with amyotrophic lateral sclerosis and their family caregivers: an exploration of their experiences and perspectives

$200,000 awarded to Dr. Andrea Parks at Sunnybrook Health Sciences Centre

Approximately 10% of people living with ALS will receive their diagnosis before turning 50. Younger middle-aged adults with ALS often face unique challenges regarding their family, employment, and financial responsibilities. Yet, there is limited research to better understand the complex physical, psychological, and social challenges faced by younger middle-aged adults with ALS and their families.

Dr. Andrea Parks aims to better understand these unexplored age-specific complexities. With this award, Dr. Parks will conduct a thorough review of existing knowledge about how age and life stage impact the experience of ALS, including physical, psychological, social, and spiritual aspects, as well as care needs and access to support services. Additionally, 25 younger middle-aged adults diagnosed with ALS at 55 or younger, along with 25 family caregivers, will participate in interviews to delve into their experiences.

Ultimately, Dr. Parks aims to provide a comprehensive understanding of the experiences and challenges faced by both younger middle-aged adults with ALS and their family caregivers. Her research will provide foundational knowledge that can be used to help guide the development of innovative, age-group appropriate interventions and support services for this specific population.

Dr. Parks’ career goal is to become an academic clinician-scientist, integrating clinical practice with a research program that addresses issues that significantly impact people affected by ALS and their families. This work builds upon a previous award where Dr. Parks set out to characterize the different types of psychological distress observed in ALS patients, with the long-term goal of developing a routine screening tool to enhance early identification of psychological distress and guide appropriate management strategies. Dr. Parks brings a unique expertise to the field that will help provide Canadians living with ALS the highest quality of care. While completing this fellowship, she will also be working towards a PhD in Clinical Epidemiology and Health Care Research.

2023 ALS Canada-Brain Canada Trainee Awards

Can a combination of advanced brain imaging and artificial intelligence uncover a biomarker to better track disease progression?

Investigating disease progression and survival outcomes in ALS patients using deep learning and deformation based morphometry

$78,000 awarded to Dr. Isabelle Lajoie, a postdoctoral fellow in Dr. Mahsa Dadar’s lab at the Douglas Hospital Research Centre, McGill University

Previous imaging studies have uncovered changes in certain brain regions of people living with ALS. The extent and location of these changes, however, can differ significantly from person to person. This has led researchers to question whether the variability in brain atrophy patterns is linked to the diversity in symptoms often observed in people with ALS, such as age of onset, disease duration, cognitive changes, and more. If such a link exists, measuring these brain changes could provide a non-invasive way for health care professionals to monitor disease progression more accurately and possibly even predict future clinical symptoms and survival outcomes.

Deformation-based morphometry (DBM) is a sensitive method for quantifying changes in various brain regions using magnetic resonance imaging (MRI). With this award, Dr. Lajoie will take advantage of comprehensive data sets already collected through national initiatives such as the Canadian ALS Neuroimaging Consortium (CALSNIC) and the Comprehensive Analysis Platform To Understand, Remedy, and Eliminate ALS (CAPTURE ALS) to investigate the relationship between DMB measurements and clinical symptoms. With the help of artificial intelligence, she hopes to uncover complex patterns in the data that otherwise may have remained undetectable and explore whether DBM has potential in predicting the course of the disease.  

Through this work, Dr. Lajoie seeks to identify a much-needed non-invasive biomarker for ALS, which could change how healthcare professionals monitor and track the disease. The information gained will deepen our understanding of the mechanisms underlying disease progression, clinical symptoms, and survival, ultimately advancing our ability to effectively manage the disease.

Can this sophisticated method to measure brain activity help researchers better understand the role of hyperexcitability in ALS and its connection to symptoms?

Profiling cortical excitability in ALS using threshold tracking transcranial magnetic stimulation and multimodal biomarkers

$75,000 awarded to Liane Phung, a PhD student co-supervised by Dr. Agessandro Abrahao and Dr. Lorne Zinman at Sunnybrook Research Institute

In the intricate network of the brain and spinal cord, neurons communicate with one another via specialized chemicals known as neurotransmitters. When this signaling network functions properly, a delicate balance is maintained between excitatory and inhibitory chemicals. A hallmark feature of ALS, thought to occur even before symptoms appear, is that motor neurons in the brain become overexcited (or hyperexcitable). This change occurs at the cellular level and can’t be noticed by people who experience it, but researchers have found evidence of hyperexcitability in both electrical recordings from the brain and markers in the cerebrospinal fluid of people with ALS. The relationship between hyperexcitability and clinical symptoms, however, remains unclear.

With this award, Liane will explore the link between hyperexcitability in ALS and various clinical and neuroimaging parameters, in addition to a fluid-based biomarker. Excitability circuits of the brain will be assessed using threshold-tracking transcranial magnetic stimulation (TT-TMS), a non-invasive technique that uses a magnetic field to stimulate nerve cells. In the first aim, Liane will analyze data from a group of 100 healthy controls to establish “normal” values for various TT-TMS parameters. She will then assess the reliability of these different TT-TMS measurements in a smaller group of 20 individuals living with ALS over a three-day period. Finally, she will seek to identify specific clinical profiles associated with hyperexcitability by comparing TT-TMS measurements from 30 individuals with ALS with demographic, neuroimaging, and clinical data (such as ALSFRS-R scores and blood neurofilament light levels – a biomarker for neurodegeneration).

This research could help to validate TT-TMS as a method to detect non-invasive biomarkers for ALS, aiding in diagnosis and potentially leading to more personalized treatment options in the future. Efforts to identify specific disease profiles, or subgroups, based on hyperexcitability may also help to improve clinical trial design, as the ability to enroll participants by specific ALS subtypes would reduce heterogeneity and therefore enhance the likelihood of detecting treatment effects.

Do acute viral infections play a role in triggering onset or accelerating the progression of ALS?

Determining the contribution of acute viral infection on the onset and progression of ALS

$25,000 awarded to Art Marzok, a PhD student in Dr. Matthew Miller’s lab at McMaster University

Both genetic and environmental factors are believed to influence the onset and progression of ALS, accounting for some of the differences we see in people living with the disease. Viral infections represent one potential environmental risk factor. For example, emerging evidence suggests that endogenous retroviruses like HERV-K, remnants of viral DNA passed down from our ancestors’ past infections, may promote inflammation and motor neuron degeneration in a subset of ALS cases. However, very little is known about the role acute viral infections may play in contributing to the onset of ALS, which are sudden and rapid infections, such as those caused by influenza and coronaviruses.

With this award, Art will investigate whether acute viral infections contribute to the onset or accelerate the progression of ALS symptoms. This work builds upon his previous studies, which showed that mice carrying an ALS-associated mutation (SOD1) and previously exposed to influenza A had an accelerated disease course compared to their uninfected counterparts. Even mice exposed to inactivated virus displayed the same accelerated symptoms, suggesting that the immune response triggered by the infection played a critical role in worsening the disease.

In this study, Art will continue his investigations in mice, seeking to unravel the mechanisms through which viral infections influence ALS. He will also broaden the scope of his research to include SARS-CoV-2, the virus responsible for COVID-19, to explore its impact on ALS progression. This project will provide novel insights into the role of acute viral infections in ALS, which could pave the way for future therapeutic and preventive strategies.

Can a better understanding of how this particular protein influences overall protein production in cells offer insights into treating ALS?

Defective protein translation: a causative pathway in ALS?

$75,000 awarded to Amrita, a PhD student in Dr. Neil Cashman’s lab at the University of British Columbia

In the vast majority of ALS cases, there is an abnormal accumulation of a protein called TDP-43 within neurons. TDP-43 plays a crucial role in processing messenger RNA (mRNA) molecules, which serve as a genetic blueprint for protein synthesis at specific cellular structures called ribosomes. When TDP-43 moves from the nucleus (where it is normally found) to the cytoplasm, a hallmark feature of ALS, it is no longer able to perform its normal function effectively. However, the precise mechanisms underlying how TDP-43 contributes to ALS are not fully understood, making the development of effective therapies challenging.

Previous studies have indicated that a buildup of cytoplasmic TDP-43 leads to a decrease in overall protein production in cells. Research conducted in the Cashman lab highlighted a potential therapeutic role for a specific ribosomal protein called Receptor of Activated C-Kinase 1 (RACK1), as it was shown that lowering RACK1 levels can reduce TDP-43 accumulation in the cytoplasm, partially relocate TDP-43 back to the nucleus, and restore normal protein production within cells. These findings suggest a novel disease mechanism whereby TDP-43 pathology is mediated by RACK1.

With this award, Amrita aims to delve deeper into the relationship between RACK1 and TDP-43 in ALS. Her research will focus on understanding how reduced RACK1 levels promote the restoration of protein production in cells and whether lowering RACK1 expression in fruit fly models of ALS can prevent neurodegeneration. The outcomes of this study could lay the groundwork for exploring RACK1-based therapies for ALS in the future and improve our understanding of mechanisms related to TDP-43 pathology, the specific role of RACK1 in ALS, and more broadly shed light on protein production defects in neurodegenerative diseases.

Will this novel decision aid improve early care planning and symptom management in those experiencing bulbar ALS symptoms?

Development of a shared decision-making aid for bulbar symptom management in ALS

$50,000 awarded to Anna Huynh, a PhD student in Dr. Yana Yunusova’s lab at Sunnybrook Research Institute

Bulbar symptoms, impacting speech and swallowing, are among the most challenging aspects of ALS. Early care planning, especially for bulbar symptoms, is vital to maintain function and quality of life for as long as possible. However, treatment decisions regarding bulbar symptoms heavily rely on personal preference, such as the use of augmentative and alternative communication (AAC) devices and feeding tube placement. These choices are often postponed due to the complexities of the disease and their personal nature, causing individuals with bulbar ALS to delay these decisions until symptoms are fully evident, resulting in multiple competing care priorities.

Decision aids are valuable tools for facilitating preference-sensitive decisions and improving communication between healthcare professionals and patients regarding treatment options. Despite their growing use in the context of ALS, there remains a gap in resources available to support shared decision-making in the management of bulbar symptoms.

With this award, Anna seeks to develop a specialized tool to facilitate decision-making conversations about bulbar symptom management between individuals with ALS, their caregivers, and healthcare professionals. Through interviews, Anna will gain a better understanding of the decision-making process for bulbar symptom management, allowing her to create a tool that considers individual needs and values. She will then develop and refine a prototype decision-making aid to be tested in an ALS clinic, collecting real-world feedback, and assessing user experience.

This work seeks to provide a well-informed and standardized approach to decision-making tailored to the management of bulbar symptoms in ALS. Decision-aids have also been shown to improve professional-patient interactions and ensure decisions align with individual and family values. Thus, this tool has the potential to significantly enhance care for those living with bulbar ALS.