The ALS Society of Canada’s (ALS Canada) vision is a future without ALS. To achieve this vision, new treatments that can help with symptom management and slow down and someday stop the progression of amyotrophic lateral sclerosis (ALS) need to undergo clinical trials on humans to ensure that they are both safe and effective before being approved for widespread availability.
ALS Canada’s work is empowered by community. Discover how, in 2023, our collaboration with clinicians and investments in research aims to enhance care and the potential for future treatments.
CALS Research Network: Connecting Canada’s clinicians and researchers
As a national convenor of the ALS community, ALS Canada was proud to provide the foundational funding to establish the Canadian ALS Research Network (CALS) in 2008. The network was established to formally unite clinician researchers and to demonstrate to the pharmaceutical industry the benefits of bringing clinical trials to the country.
Recognizing the significance and effectiveness of CALS in uniting clinicians in Canada to accelerate research and improve care for people affected by ALS and their families, ALS Canada assumed administrative management of the network in 2017.
“CALS informs all areas of our mission as a trusted source the ALS community can rely on,” says Colleen Doyle, Senior Manager of Research and CALS at ALS Canada. “These are the experts doing the work in our communities, whether in a clinical setting or within the lab, working to advance what we know about the disease and potential treatments.”
Over the past five years, CALS has grown significantly, doubling its membership and extending its reach across Canada. This growth has strengthened its ability to collaborate effectively as a network, providing opportunities to mentor early career clinicians, partner more closely with pharmaceutical companies to bring promising clinical trials to Canada, and support grassroots research efforts led by physicians. Since its inception, more than 35 ALS clinical trials have taken place at CALS centres across the country.
These efforts have helped develop resources to assist people living with ALS, clinicians, and allied health professionals. This includes ReferALS, designed to help general neurologists recognize ALS symptoms earlier and refer potential cases to a CALS clinic. By speeding up the diagnosis process, ReferALS ensures quicker access to vital care, approved treatments, and the possibility of participating in clinical trials, all of which can make a significant difference in slowing down the progression of the disease and enhancing the quality of life.
In 2023, ALS Canada surveyed CALS members to gain insights into their communities’ support and healthcare services. Thanks to the collaborative nature of its membership, the survey had a high response rate and will help identify gaps and barriers faced by people living with ALS. With this valuable data, ALS Canada and our partners are better equipped to advocate government for improvements and ensure equitable access to care for everyone affected by ALS.
Drawn to the mysteries of ALS research
It was the mystery surrounding the disease that drew Dr. Alex Parker to ALS research. Since his grad school days, he has had a deep interest in neurodegenerative diseases, their onset, progression of symptoms, and their variation between each person diagnosed.
To help solve this mystery, Dr. Parker’s team at the Department of Neuroscience at the Centre de recherche du CHUM at Université de Montréal is investigating the microbiome, a natural collection of bacteria and other microbes that play a crucial role in maintaining our health, including possibly our brain and spinal cord. The team has developed simple ALS models using worms to better understand how motor neurons degenerate and explore whether
Thanks to the support of the ALS Canada Research Program, in partnership with Brain Canada, the team has made significant progress in its research. Investigating the effects of probiotics has the potential to lead to new ALS therapies, and this area of study has successfully led to clinical trials for other diseases. In Dr. Parker’s lab, certain probiotics have been found to be protective in the ALS models, one of which will be tested in an upcoming clinical trial. These trials could provide promising new clues to unlocking the mysteries of this terrible disease.
“Although I spend most of my time in the lab, I know that figuring out ALS is more than an academic exercise. It is a race against time for people living with the disease,” says Dr. Parker. “The speed at which ALS progresses can be fast, and it’s almost always devastating, so I appreciate that the ALS community needs answers as soon as possible.”
Learn more about our work in 2023 by exploring our latest annual report.
Canada continues solidifying its reputation as a leader in ALS research innovation, as evidenced by the magnitude and quality of conversations, knowledge sharing, and relationship building at the 2024 ALS Canada Research Forum. From April 27 to 29, researchers, industry partners, ALS Canada supporters, and more attended the in-person, three-day event, that aimed to move the needle on research toward effective therapies and avenues to improve the quality of life for people affected by ALS.
The weekend kicked off with a keynote presentation by neurologist Prof. Orla Hardiman on PRECISION ALS, a pan-European collaborative platform that brings together researchers, industry experts, and more to accelerate drug discovery and treatment for ALS. Later that evening, attendees heard from community members Mehboob and Sophie Damji. They also learned more about the global work of the International Alliance of ALS/MND Associations from the CEO, Cathy Cummings, and the role ALS Canada plays in working toward a world free of ALS.
Throughout the weekend, attendees were treated to engaging presentations from researchers of all levels, including students, doctoral candidates, postdoctoral fellows, and senior researchers and clinicians. Session topics were diverse – from using virtual reality to improve breathing in people living with ALS, to identifying environmental risk factors for ALS, to poster presentations by up-and-coming junior researchers, to a panel discussion led by seasoned researchers on what makes a great principal investigator. These presentations and conversations further cemented the ALS research community’s deep-rooted commitment to finding a cure for ALS through collaboration and partnership.
For Canadian ALS Learning Institute graduate and ALS Canada Community Ambassador Andrew Dundas, the Research Forum was fascinating and an opportunity to share his lived experiences with researchers. “I’m hoping to understand the research [on] not only for advancement and the cause of ALS, ultimately [to find] a cure, but also for opportunities to improve the quality of life for patients with ALS like myself while a search for a cure is found.”
Andrew reminds us of the reason knowledge-sharing events like the ALS Canada Research Forum are needed – to foster hope, collaboration, and solutions in the pursuit of creating a world free of ALS. He reminds us that finding a cure is not the only goal to strive for and that working towards improving quality of life is just as important.
For Jenny Zhang, a junior researcher at the University of Ottawa and the winner of the Research Forum’s Minute to Win It and poster competitions, the event was a valuable experience that allowed her to network and receive feedback on her work. “As someone currently exploring potential career possibilities, the 2024 ALS Research Forum allowed me to learn more about various ALS research pathways that I wasn’t aware of…All of these experiences will support my progress and improve my work.”
Jenny also echoes the sentiment of many Research Forum attendees that collaboration is critical for advancing ALS research. “I believe that uniting researchers with varying scientific backgrounds and perspectives can help drive innovation and speed up the development of treatments for complex diseases like ALS,” she said. “Bridging together researchers and clinicians and people living with or affected by ALS has provided a sense of hope for the community to continue making progress in ALS research and improve quality of life.”
The 2024 ALS Canada Research Forum is made possible thanks to generous support from our platinum sponsor, Mitsubishi Tanabe Pharma Canada; our gold sponsor, Amylyx Pharmaceuticals; and our silver sponsors, Biogen and QurAlis. We thank our sponsors for their support and generosity in fostering collaboration, knowledge sharing, and capacity building at the 2024 ALS Canada Research.
This glossary contains a list of scientific and medical terms and definitions that are relevant to amyotrophic lateral sclerosis (ALS). It can be used by anyone from within the ALS community including recently diagnosed individuals, caregivers, medical professionals, researchers, as well as by the general public. The research glossary was developed to help support knowledge-sharing by helping to provide clarity around terminology that may be unfamiliar to our readers.
Amyotrophic lateral sclerosis (ALS) is a complex disease with varying symptoms and severity for people affected. Due to its heterogeneity, diagnosing the disease can be challenging and finding effective treatments can also be difficult.
Through a collective effort, researchers aim to better understand the genetic causes of ALS, identify biomarkers for early detection, and impact how clinicians can treat the disease.
Participating for future generations
Looking back, Kris Noakes can see how her genetic form of ALS has impacted her family through generations. Living with the disease has meant letting go of parts of her life, including her love for running and reimagining her career.
After Kris recovered from the initial shock of her diagnosis, she turned to her First Nations teachings for guidance. Embracing her feeling of responsibility for the community, she is determined to assist in research, advocacy, and support for people like herself living with ALS.
Kris journeys to Sunnybrook Hospital in Toronto four times a year, where the team looks at the progression of the disease, and she undergoes MRI scans, cognitive and speech testing, and has her blood collected.
“People aren’t necessarily thinking of this at the time of diagnosis,” Kris shares. “It’s half a day that can really have an impact on our lives. It’s a small sacrifice to help lead us to finding a cure for this devastating disease.”
Samples and data are de-identified and will be shared globally for researchers to use for scientific advancement. Kris believes the more her samples are used, the better. She likes the idea of her samples travelling around the world and going to the places she might not have the opportunity to see in her lifetime.
“People can study me any way they want. My life depends on it; how can I not participate? My children’s lives, my cousins. The clock is ticking,” she adds.
Importance of personal engagement
CAPTURE ALS prioritizes the voices of people affected by ALS, their families, friends, and communities. It has an active Participant Partner Advisory Council (PPAC) that advises on research priorities, participant recruitment, and engagement guidelines.
“By including the voices of people living with ALS, the research gains an elevated sense of purpose and urgency,” said Shelagh Genuis, a CAPTURE ALS member who works with the PPAC. “Research projects sometimes fall behind schedule, but for someone living with ALS, every day counts. With their presence on our council, researchers are reminded of the time-sensitive nature of their work and are motivated to prioritize the needs of people affected by the disease.”
Participant engagement has been a priority since the beginning of the initiative. Early consultation with focus groups of people living with ALS and family members informed and shaped the funding application, including study design and CAPTURE ALS’ data sharing plan. Today, their participation ensures that the lived experience is embedded in all the research the team engages in.
Healthy Canadians are also needed in research
The ALS Society of Canada (ALS Canada) is proud to support CAPTURE ALS, and our team is actively participating in it. Carolina Jung, research specialist at ALS Canada, recently participated in the study as a healthy control participant.
“Healthy controls are an important part of any research study,” Carolina shared. “For researchers to obtain reliable and impactful results, they need healthy volunteers to participate. It’s a small contribution of your time and effort that can ultimately have a huge impact on people living with ALS.”
Join CAPTURE ALS
The team at CAPTURE ALS is seeking people living with ALS, their families, and control participants who can travel to clinics located near Edmonton, Toronto, Montreal, or Quebec City. To learn more about getting involved, visit captureals.ca.
On World Science Day, the latest ALS Canada-Brain Canada research awards, with support from Fondation Vincent Bourque, highlight the importance of funding early-career researchers and clinicians
Toronto — In recognition of World Science Day, together with Brain Canada, the ALS Society of Canada (ALS Canada) is pleased to announce the 2023 ALS Canada-Brain Canada Clinical Research Fellowship and Trainee Award recipients. These early career grants are designed to support the training and research of clinicians in clinical care and PhD students and postdoctoral fellows engaged in research related to amyotrophic lateral sclerosis (ALS) across Canada.
With an estimated 3,000 Canadians living with ALS, investing in the next generation of researchers is critical to learning more about the disease, improving therapies, and eventually finding a cure.
“Our commitment to invest in clinicians and researchers early in their careers through the Clinical Research Fellowship and Trainee Award programs ensures that we have top medical and scientific talent working hard to find treatments for people living with ALS,” said Dr. David Taylor, Vice-President of Research and Strategic Partnerships, ALS Canada. “These are critical parts of our national Research Program that drive optimal care and discovery toward our vision of a future without ALS.”
“Investing in the future of ALS research means investing in the brilliant young minds who possess the insights needed to unravel the complexities of the disease,” says Dr. Viviane Poupon, President and CEO of Brain Canada. “Through the Clinical Fellowship Award and the Trainee Award program, Brain Canada proudly supports these up-and-coming scientists, as they are shaping a more hopeful future for those battling ALS.”
The Clinical Research Fellowship is designed to support a clinician’s training in clinical care and research skills related to ALS, which is crucial to building better clinical infrastructure across Canada.
The Clinical Research Fellowship will provide $200,000 in funding.
Summary of 2023 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? Dr. Andrea Parks, co-supervised by Dr. Agessandro Abrahao, Dr. Lesley Gotlib Conn, Dr. Joanna Sale, and Dr. Lorne Zinman, Sunnybrook Health Sciences Centre, awarded $200,000
The Trainee Awards include two streams of funding: Doctoral students and postdoctoral fellows receive financial support to cover their salaries for up to three years, providing Canadian labs with the necessary funds to have top researchers working on the best projects to better understand the disease and drive toward new treatments for individuals living with ALS.
A total of $303,000 was awarded through the 2023 Trainee Awards.
Summary of 2023 Doctoral Awards
Will this novel decision aid improve early care planning and symptom management in those experiencing bulbar ALS symptoms? Anna Huynh, a PhD student in Dr. Yana Yunusova’s lab at Sunnybrook Research Institute, awarded $50,000 over two years
Do acute viral infections play a role in triggering onset or accelerating the progression of ALS?
Art Marzok, a PhD student in Dr. Matthew Miller’s lab at McMaster University, awarded $25,000 for one year
Can this sophisticated method to measure brain activity help researchers better understand the role of hyperexcitability in ALS and its connection to symptoms? Liane Phung, a PhD student co-supervised by Dr. Agessandro Abrahao and Dr. Lorne Zinman at Sunnybrook Research Institute, awarded $75,000 over three years
Can a better understanding of how this particular protein influences overall protein production in cells offer insights into treating ALS? Amrita Verma, a PhD student in Dr. Neil Cashman’s lab at the University of British Columbia, awarded $75,000 over three years
Summary of 2023 Postdoctoral Fellowship
Can a combination of advanced brain imaging and artificial intelligence uncover a biomarker to better track disease progression? Dr. Isabelle Lajoie, a postdoctoral fellow in Dr. Mahsa Dadar’s lab at the Douglas Hospital Research Centre, McGill University, awarded $78,000 over two years
World Science Day reminds us of the impact science has in all our lives. ALS Canada is proud to support emerging scientists and clinicians whose ideas and discoveries will advance treatment and eventually lead to a world free of ALS.
Funding for Anna Huynh’s Doctoral Award was made possible through partnership with Fondation Vincent Bourque, who generously contributed $25,000 to ALS Canada, which was matched by Brain Canada through the Canada Brain Research Fund (CBRF).
The CBRF is an innovative arrangement between the Government of Canada (through Health Canada) and Brain Canada Foundation, which increases Canadians’ support for brain research and expands the philanthropic space for funding brain research to achieve maximum impact. To date, Health Canada has invested more than $145 million in brain research through the CBRF which has been matched by Brain Canada Foundation and its donors and partners.
About ALS Canada and the ALS Canada Research Program
The ALS Society of Canada (ALS Canada) is working to change what it means to live with amyotrophic lateral sclerosis, an unrelenting and currently terminal disease.
Grounded in and informed by the Canadian ALS community, we respond to the urgent unmet need for life-changing treatments by investing in high-quality research that will fuel scientific discovery and by engaging industry, supporting increased clinical capacity and advocating for equitable, affordable, and timely access to proven therapies.
Responding to the tremendous need for current and credible ALS knowledge, awareness, and education, we empower Canadians affected by ALS to navigate the current realities of ALS, be informed consumers of ALS information, and advocate effectively for change.
Through the ALS Canada Research Program, we fund peer-reviewed research grants, foster collaboration and build capacity within Canada’s ALS research and clinical community, and invest in new areas of research positioned to have high impact. As the only national dedicated source of funding for ALS research across Canada, the ALS Canada Research Program aims to accelerate research impact by providing funding for the most promising ALS projects focused on translating scientific discoveries into treatments for ALS. We are grateful for the support of our donors and the contributions from participating provincial ALS Societies through the Walk to End ALS.
About Brain Canada
Brain Canada is a national non-profit organization that enables and supports excellent, innovative, paradigm-changing brain research in Canada. It plays a unique and invaluable role as the national convener of the brain research community. We join people, labs and platforms across the country, as well as institutions, organizations and sectors – to drive innovation and foster an interconnected brain research system. Our work enables Canada to excel and make even greater contributions to the global quest to understand the brain and brain disorders. Join us in funding brilliance daily, braincanada.ca.
About Fondation Vincent Bourque
Vincent was diagnosed with ALS in 2015. He knew that ALS was not an incurable disease, but an underfunded one. With his wife, Isabelle Lessard, and many friends, he created a Fondation to help families living with ALS and to support research in order to eradicate ALS. He passed away in 2018, but his legacy to the ALS community is immeasurable. The Fondation Vincent Bourque has raised more than $1,200, 000 since 2018, given five research grants to star researchers dedicated to ALS, and distributed more than $250, 000 to help families. The Fondation Vincent Bourque is proud to be working with ALS Canada and Brain Canada toward a future without ALS.
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After finishing his PhD in France, Dr. Ghazale moved to Canada to work with Dr. Carol Schuurmans at Sunnybrook Research Institute. Her team examines if neuronal reprogramming could serve as a potential treatment strategy for neurodegenerative diseases, including ALS.
ALS causes damage to neurons, affecting the body’s everyday ability to function. Dr. Ghazale’s work focuses on attempting to reprogram glial cells – a common and abundant type of brain cell – into new neurons. The team hopes these fresh cells could effectively integrate with existing cells in brains of people with ALS, improving their capacity and quality of life.
At the moment, Dr. Ghazale is testing the strategy in animal models. But with this influx of funding, he notes he can speed up his project timeline and do higher-tech experiments. The award will also help him refine his strategy to potentially translate this work to clinical applications.
“I know that this work could one day end up supporting people living with ALS and their families and help … ease what they’re going through,” he says. “This is what motivates me every day to keep working hard to improve therapeutic strategies.”
“We must continue to push the boundaries of ALS research,” says Dr. Viviane Poupon, President and CEO of Brain Canada. “It’s through these uncharted territories that we will uncover the solutions and enable ourselves to envision a future where ALS no longer exists.”
Funding for the 2022 Postdoctoral Fellowship was made possible by Fondation Vincent Bourque, who generously contributed $82,500 to ALS Canada, which was matched by Brain Canada through the Canada Brain Research Fund (CBRF).
The CBRF is an innovative arrangement between the Government of Canada (through Health Canada) and Brain Canada Foundation, which increases Canadians’ support for brain research and expands the philanthropic space for funding brain research to achieve maximum impact. To date, Health Canada has invested more than $145 million in brain research through the CBRF which has been matched by Brain Canada Foundation and its donors and partners.
The ALS Canada-Brain Canada Trainee Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
Meet the students who received the 2022 ALS Canada – Brain Canada Doctoral Awards
PhD student Lucia Meng Qi Jadon (previously Liao) is the recipient of a $75,000 ALS Canada – Brain Canada 2022 Trainee Award. She will use the funding to investigate whether a newly discovered tag on TDP-43 might have an important role to play in ALS.
For her first six months of doctoral work in Dr. Dale Martin’s lab at the University of Waterloo, Lucia struggled. “I was trying to show something that hadn’t been shown before, so it was difficult,” she said.
But then – success. She detected a faint signal that confirmed she was on the right path. Thanks to her persistence, her work is opening up a new pathway for research.
In a way, the award was like that first signal, confirming her work as a researcher. “I put in all this work, and this award helps me know I’m good enough to be here,” she said. “It’s a huge encouragement that I am cut out for this.”
Lucia’s desire to understand the intricate, complex processes of human cells drives her passion for research.
“When you discover one process, it immediately opens up new possibilities. It’s like a puzzle you keep finding more pieces to,” she says.
Lucia’s project looks at one piece of the complicated ALS puzzle. Early in her PhD work, she confirmed that TDP-43 undergoes a modification called palmitoylation. This process may play a role in TDP-43 mislocation, one of the most common hallmarks of ALS.
She will use this funding to better define the properties of palmitoylation of TDP-43 and understand how it might be abnormal in ALS.
“I’m peeling back the layers, little by little,” she says.
“Ms. Jadon’s work will serve as a beacon, drawing the attention of like-minded scientists eager to explore new frontiers in ALS research,” says Dr. Viviane Poupon, President and CEO of Brain Canada.
Lucia says looks forward to sharing her findings to spark new collaborations within the ALS research community. “I want to establish the basics of this information I discovered and get this out there,” she said. “Then other researchers will know this is something they may want to look into.”
The ALS Canada-Brain Canada Trainee Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
Meet the students behind the 2022 ALS Canada – Brain Canada Trainee Awards
Charlotte Manser is the recipient of a $75,000 ALS Canada – Brain Canada 2022 Trainee Award. As a PhD student at the University of Ottawa, she investigates how ALS-linked genes might contribute to the loss of normal stress granule formation.
When our cells are stressed, they create “stress granules” to protect RNA, which are critical substances to cellular health. Charlotte explores how the abnormal accumulation of stress granules might contribute to the mislocation of the protein TDP-43, a common hallmark of ALS.
She has tested many genes that might be linked with both stress granule formation and ALS.
“I found two hits that I’m actively pursuing,” she says. “With these, we can try to uncover new mechanisms of disease or a new therapeutic target. They can help us better understand how the disease comes about.”
Determination motivated by loss
Charlotte’s work is motivated by her personal connection to the disease.
In 2013, her father died from ALS. Around that time, she switched her undergraduate major from forensics to neuroscience.
“It was a light bulb moment,” she says. “I knew this is what I wanted to do.”
She also became an active member of the community of families affected by ALS. Charlotte notes that it means a lot for this same community to recognize her work with this award.
“This work represents the hope of turning something awful, like grief, into something productive and positive,” she says. “My hope is that I can contribute something to the field so that it isn’t so bad for the next person.”
The ALS Canada-Brain Canada Trainee Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
ALS researchers from around the world continue to build upon existing work and make new discoveries in the hopes of realizing a future without ALS. In the October 2023 Research Update, you’ll learn about advances in understanding the presymptomatic stage of ALS, new guidelines for genetic testing and counselling, an experimental cell replacement strategy, new insights into cellular pathways disrupted in ALS, and more.
We recently developed a research glossary that contains a list of scientific and medical terms and definitions relevant to ALS. The glossary was created to support knowledge-sharing by helping to provide clarity around terminology that may be unfamiliar to our readers. Click here to download a copy.
Uncovering early blood biomarkers for ALS: A promising step towards timely intervention
Researchers have identified specific blood biomarkers that may signal changes prior to symptom onset in ALS.
Multiple lines of evidence suggest that metabolic alterations occur several years before the onset of ALS symptoms. For example, a previous study showed a consistent reduction in metabolic activity among presymptomatic ALS gene mutation carriers compared to healthy controls.
In this UK-based study, researchers analyzed blood tests obtained during routine health screenings from individuals who later received an ALS diagnosis. Using complex statistical methods, they compared a range of blood markers, including cholesterol levels and triglycerides, with those from a healthy control group. The analysis revealed a pattern: individuals with ALS experienced metabolic changes, specifically a decline in both total cholesterol and low-density lipoprotein cholesterol, well before the onset of symptoms and several years ahead of their formal diagnosis. Notably, in recent years, other research groups have identified altered, but different, metabolic markers prior to symptom onset.
While researchers note that further studies are required to better understand the relevance of these findings at the individual level, the results provide further evidence for the existence of a presymptomatic phase in ALS characterized by metabolic changes. The ultimate goal is to discover a highly sensitive early warning signal for ALS, so that intervention can take place before irreversible motor neuron damage occurs. This work represents an important step in that direction.
With increasing knowledge of the genetic causes of ALS, research centered on the presymptomatic stage has become a prominent area of interest in the field. ALS Canada recently sponsored and participated in a workshop co-hosted by the ALS Hope Foundation and Genetic ALS & FTD: End the Legacy that focused on identifying gaps in knowledge in this area and developing guidelines for the clinical management of individuals genetically at risk for ALS. This shift in thinking, with a strong focus on the presymptomatic phase, is critical to reshaping the way we approach ALS treatment in the years ahead.
Development of genetic testing guidelines for ALS to promote standardized care and support
An expert panel have developed guidelines to support all stakeholders in the ALS community in navigating the benefits and challenges of genetic testing.
Significant strides have been made in unraveling the genetic underpinnings of ALS. Earlier this year, the FDA granted approval for the first targeted genetic therapy, known as tofersen or Qalsody, designed to treat SOD1-linked ALS. Genetic factors have also been shown to play a role in some sporadic (non-inherited) ALS cases. As research and care in this area continue to advance, it’s critical that genetic testing practices keep up with these developments.
In this study, researchers used a systematic approach to develop a set of guidelines to improve and standardize genetic counselling and testing practices among healthcare providers. A total of 35 guideline statements were developed. Briefly, the guidelines recommend that all people living with ALS should be offered genetic testing for, at a minimum, the four most common ALS genes: C9ORF72, SOD1, FUS, and TARDBP. Specific education and risk assessments that should be provided before and after testing are also identified, along with instructions for laboratories conducting the tests.
These evidence-based guidelines will help to ensure that everyone involved in the ALS community better understand the advantages and complexities of genetic testing. With gene-targeted clinical trials ongoing for several other ALS-associated genes, these guidelines are timely and will help to promote fair access to genetic testing and gene-targeted treatments when available (and applicable). In line with the rapid advancements in this area, ALS Canada is working to develop a central hub on our website to provide more comprehensive and centralized information on ALS genetics. Stay tuned for more information.
Advances in a cell replacement strategy to restore neuromuscular function in ALS
Scientists have developed a technique to transplant healthy nerve cells into mice with an aggressive form of ALS.
The neuromuscular junction (NMJ) is a vital connection point where motor neurons, the nerve cells responsible for voluntary muscle movements, communicate with muscle fibers. Many researchers believe that one of the earliest events in ALS is the detachment of motor neurons from muscle fibers at the NMJ.
In this study, researchers set out to develop a strategy to help restore muscle function in ALS. Using a mouse model, healthy motor neurons derived from stem cells were placed near target muscles. The transplanted neurons were able to form connections with nearby muscle cells, however, they were not integrated into the body’s natural neural pathways through the brain and spinal cord. As a result, external activation was required to stimulate these neurons to pass signals to muscle cells, and this is where a technique called optogenetics played an important role. Using this technique, researchers were able to trigger motor neuron activity by shining a specific type of light on the cells.
Initial experiments faced challenges with the immune system attacking the transplanted cells, however, a specific therapy called H57-597 prevented rejection and allowed healthy connections to be made between neurons and muscles. With regular stimulation, researchers found that muscle connections in the mice grew stronger, resulting in more powerful muscle movements and reduced muscle wasting.
Though these findings are interesting, it’s important to note that the research was conducted in mice, and further studies are needed to determine if this approach can be translated to humans. The long-term vision involves the potential use of implantable devices to deliver the required external stimulation for muscle activity. Ultimately, this work offers hope for the development of a novel cell therapy that could potentially benefit people living with ALS in the future.
Insights into the role of NEK1 and its therapeutic potential in ALS
New research uncovers the cellular pathways affected by NEK1 gene mutations in ALS, providing important foundational knowledge for considering NEK1 as a future therapeutic target.
In 2016, an international team of researchers, including Canadian scientists, first identified NEK1 as a gene associated with ALS. Mutations in NEK1 account for 2 to 3% of both familial and sporadic ALS cases. Yet, the mechanisms through which these mutations contribute to motor neuron dysfunction remain unknown.
In this study, researchers utilized motor neurons derived from individuals carrying NEK1 mutations and fruit flies to model the disease. The results showed that NEK1 mutations disrupt two vital cellular pathways: the microtubule cytoskeleton and nucleocytoplasmic transport (NCT). NEK1 mutations were found to interfere with the function of microtubules, which are essential components to maintaining the structural integrity of a cell. Furthermore, these mutations were found to also affect NCT, a process that involves the exchange of substances between two important compartments of the cell – the nucleus and cytoplasm. Both pathways play a critical role in ensuring the cell’s survival and have been implicated in ALS in many other studies.
Specific anticancer medications, like paclitaxel and the experimental treatment laulimalide, are known to halt cell division by stabilizing microtubules. The researchers decided to test the potential of these drugs in the context of ALS and found that these compounds were effective in restoring the deficits linked to NEK1 mutations in both pathways. This suggests a possible connection between the two cellular processes.
It’s important to emphasize that these cancer drugs can be highly toxic, with a lengthy list of side effects, and may not be suitable for ALS treatment. Nevertheless, this study provides valuable insights in the role of NEK1 in ALS and provides proof-of-concept that stabilizing microtubules could hold potential as a therapeutic approach for ALS. Researchers are now working to better understand exactly how NEK1 regulates these pathways in human neurons, which is important to inform future treatment strategies.
New research sheds light on widespread RNA and protein misplacement in ALS
A new study reveals that protein and mRNA mislocalization within ALS-affected motor neurons may be more widespread than previously thought.
In ALS, proteins like TDP-43 often move from their usual location in the cell’s nucleus (the central hub housing DNA) to the cytoplasm (the region outside the nucleus), where they tend to aggregate into clumps and no longer function properly. Recent findings suggest that this misplacement issue is widespread, extending beyond a few proteins and including mRNA molecules, which play an important role in delivering instructions for protein synthesis from DNA located within the nucleus.
In this study, researchers used stem cells derived from ALS patients with mutations in two ALS-linked genes, TARDBP and VCP, to create motor neurons in the lab. They separated the cell into its two primary compartments, the nucleus and the cytoplasm, and analyzed the distribution of both mRNA and protein within each. They discovered that the ALS-affected motor neurons exhibited significant mislocalization of hundreds of mRNAs and proteins compared to healthy cells.
The movement of these mRNAs and proteins between the nucleus and cytoplasm hints at issues with the cell’s internal transport mechanisms. Additionally, the mislocalized mRNAs and proteins tended to interact more with each other compared to their correctly positioned counterparts. This suggests that as these mRNAs and proteins mislocalize, they might inadvertently drag each other along, creating a domino effect within the cell.
In an attempt to restore normal protein and mRNA localization, researchers tested an experimental therapy called ML240, which is designed to block the activity of the VCP enzyme. They found that it partly corrected mislocalization and reduced DNA damage, indicating that VCP inhibition may have therapeutic potential in ALS.
The researchers note that future studies are needed to validate these findings in different ALS genetic backgrounds and models. Regardless, this work represents a shift in our understanding of ALS, revealing that it involves not just the abnormal movement of a handful of proteins, but rather the widespread mislocalization of numerous proteins and mRNAs, opening up new avenues for research and potential treatments.
Note: We have included links to the publications because we know you may be interested in the original source papers. While abstracts are always available, many journals are subscription based, and in some cases, full papers may only be accessed at a cost.
Meet the junior researchers who received the 2022 ALS Canada – Brain Canada Trainee Awards
Donovan McDonald is the recipient of a $75,000 ALS Canada – Brain Canada 2022 Trainee Award. As a PhD student, he investigates how the function of tRNA could contribute to ALS disease processes.
Donovan came to Canada from the Bahamas. “People don’t always recognize the challenges that international students face,” he says. Funding opportunities, for example, can be far more limited.
Award programs like those provided by ALS Canada and Brain Canada help fill a critical funding gap for promising students like Donovan.
“Supporting international students in brain research is vital for fostering diverse perspectives, advancing global scientific collaboration, and accelerating breakthroughs in understanding the complexities of the brain,” says Dr. Viviane Poupon, President and CEO of Brain Canada.
“It’s not just about the money,” Donovan says. “It’s also having your research recognized. This is crucial to your development as a scientist.”
Donovan’s original project sought to understand basic biological processes around tRNA. This critical molecule acts as a master key within cells to help proteins form. But working alongside prominent ALS researchers at Western University, he realized how relevant his work could be to exploring “uncharted territory” in ALS research.
In particular, Donovan is exploring how tRNA dysfunction might contribute to ALS in relation to a protein called angiogenin. Researchers have linked mutations in angiogenin, which helps regulate tRNA, to genetic cases of ALS.
“Despite being known for a long time, very few studies look at angiogenin and its role in ALS. That’s where I come in,” Donovan says.
The young researcher hopes his work helps others recognize to the idea that tRNAs are important molecules to study in ALS.
“I want to unravel how tRNA dysfunction can help point to either development of or predisposition to ALS,” he says. The ALS Canada – Brain Canada Trainee Award will help him do just that.
The ALS Canada-Brain Canada Trainee Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
Meet Dr. Philip McGoldrick, recipient of the 2022 ALS Canada – Brain Canada Career Transition Award
Dr. Philip McGoldrick, a researcher at the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto, is the 2022 recipient of a $250,000 ALS Canada – Brain Canada Career Transition Award.
This award helps launch talented early-career researchers, allowing them to set up their own labs, giving them the independence to establish their own research programs.
“This award enables me to continue something I’ve been passionately working on for several years,” he says. “The work I am doing is so exciting. It would have been a huge loss to not be able to continue it.”
Dr. McGoldrick was inspired to study neurodegenerative disease at a young age after seeing how these types of diseases affected family members. After moving to London (UK) for a PhD, ALS soon caught his interest.
“It was the most interesting one of the diseases being studied,” he says. He’s been working in ALS since 2008.
Dr. McGoldrick studies mutations in the C9ORF72 gene – the most common genetic cause of ALS. His current projects explore how the loss of function that occurs when C9ORF72 is mutated can affect a crucial biological process called nucleocytoplasmic transport. He and his co-researchers recently published an article on the topic in Cell Reports. He is also interested in how these insights could be helpful in understanding sporadic cases of ALS.
“This support will allow me to investigate a fundamental but understudied mechanism that may contribute to ALS,” he says. “My hope is that I can be part of a sustained effort on multiple fronts to understand a genetic cause of ALS, but also apply these findings to understand sporadic disease too.”
“This transformative program and collaboration with ALS Canada has the potential to inspire early-career researchers to explore innovative approaches, which could lead to a future without ALS,” says Dr. Viviane Poupon, President and CEO of Brain Canada.
The ALS Canada-Brain Canada Trainee Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
ALS Canada’s mission is to improve the lives of people affected by ALS through support, advocacy, and investment in research for a future without ALS.
Meet the researchers behind the winning 2022 Discovery Grant projects
Could protecting the axon represent a promising treatment strategy for ALS?
Award: $300,000
Collaborators: Dr. Gary Armstrong, McGill University
Dr. Alex Parker, at the Centre de recherche du CHUM, Université de Montreal, is one of the first two recipients of the newly introduced three-year, $300,000 ALS Canada-Brain Canada Discovery Grant. Dr. Parker’s grant was funded in generous partnership with Dr. Jean-Pierre Canuel Fund – SLA Québec.
Dr. Parker’s project looks at possible targets for slowing neuronal degeneration in small worms used to model ALS, called C. elegans, which he has worked with since his days as a doctoral student at the University of British Columbia. He has been fascinated by neurodegeneration even as an early career researcher.
“I liked the idea of trying to model neurodegeneration in a simple system,” he says. “You can go fast and find things.”
He started his work looking at Huntington’s Disease before switching to ALS – a challenging disease that motivates him to work on problems not everyone wants to tackle.
“ALS is not like other diseases. It’s a hard problem – the disease window is short and aggressive,” says Dr. Parker. “For many people, it seems intractable. But we’re keeping at it – and I think we can make a contribution.”
For decades, researchers have used worm models to understand which genes help regrow neuronal axons after they are damaged. To date, these genes have not been studied for their role in the damage done by ALS.
Dr. Parker began this project by cataloging more than 100 of these genes – which either promote axonal regrowth or slow further damage – as potential targets for study in ALS models.
“We tested them all. And lo and behold, some of them actually stopped further neurodegeneration in an ALS model,” he says.
He then tested his “short list” on older worms that better simulate the cellular environment of ALS patients, who tend to be diagnosed in midlife or later. The result was two “extremely potent targets for slowing neurodegeneration,” he notes.
“We’re taking biology that’s known and rephrasing it for ALS,” Dr. Parker explains. The hope is to find drugs that can target these genetic pathways that reignite a cell’s ability to regenerate its own axons, effectively slowing disease progression.
He said the upgraded funding opportunity helped him think more ambitiously about the project and bring in collaborators that could accelerate the research.
Dr. Parker is working with Dr. Gary Armstrong at McGill University, an expert on zebrafish models. With the larger funding amount, Dr. Parker can move his hypothesis through different levels of validation, including zebrafish and iPSCs (human cell models), which could allow him to advance his findings to clinical trial on a much shorter timeline.
“The structure of the grant opened up the possibility of pushing this further and faster,” he says. “We’re already moving towards validation, and we just started.”
“This type of program is so important,” he adds. “It funds projects at the early stages, when it’s more challenging to get funding. This ALS Canada-Brain Canada Discovery Grant gave us the chance to really get our research going.”
“Supporting research at its earliest stages leads to transformative breakthroughs that have a lasting impact on human health and well-being,” says Dr. Viviane Poupon, President and CEO of Brain Canada. “By funding early-stage research, we can address critical gaps in knowledge, focus on emerging challenges, and encourage researchers to explore unconventional approaches.”
The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.
ALS Canada’s mission is to improve the lives of people affected by ALS through support, advocacy, and investment in research for a future without ALS.
“It’s always really exciting when you get a research grant, because you’re using your ideas that you’ve researched in the literature and created new experiments around,” he says. “After all that, it’s exciting to have other scientists review it and appreciate your ideas.”
This project represents his first grant for ALS research, but it builds on his decades of work studying the proteins involved in neurodegeneration, particularly in Parkinson’s disease.
“It’s a bit of a new direction for my lab, but it seems like a logical progression” says Dr. Shaw.
“At Brain Canada, we adopt the One Brain approach to research, knowing that every discovery has the potential to have an impact across a spectrum of brain diseases and disorders,” says Dr. Viviane Poupon, President and CEO of Brain Canada. “Dr. Shaw’s work in both Parkinson’s disease and now ALS will improve our understanding of the complexity of the brain as a whole.”
Tagging proteins to “take out the trash”
When our cells age, our body has a mechanism to “tag” unwanted or problematic proteins so they can be removed. Unfortunately, the enzyme machinery for this process often does not work properly in ALS and other neurodegenerative diseases.
Dr. Shaw’s project seeks to identify which proteins might be responsible for tagging the unwanted or misfolded proteins for removal from cells in common types of ALS.
“And if what we can do is identify proteins that we think are regulating these processes,” he explains, “those enzymes could be potential targets for small molecule therapeutics.”
His transition from other neurodegenerative diseases to ALS research is aided by his collaborators, including long-time ALS researchers Dr. Martin Duennwald, also at Western University, and Dr. Elizabeth Meiering at the University of Waterloo.
Though Dr. Shaw studies the most intricate of biochemical processes, he says he is inspired by the possibility that his research could make a difference for people living with ALS.
“I’ve always wanted to do research that is going to make a tangible difference, that has the potential to better people’s lives and health,” he says.
“In the long run, we are attempting to identify the root cause of diseases like ALS. These types of experiments are really important in doing that,” he adds. “This project does have the potential, I think, to impact people’s lives.”
The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.
ALS Canada’s mission is to improve the lives of people affected by ALS through support, advocacy, and investment in research for a future without ALS.
“I don’t usually do biomedical research – I usually do fundamental biology,” she says. “This project is really exciting because it allows my research to be more meaningful.”
Her winning 2022 proposal focuses on something Dr. Vera Ugalde has studied since her earliest work as a researcher: heat shock proteins (HSPs).
When a protein misfolds in our cells, they no longer do their jobs properly or may become toxic. Fortunately, our bodies don’t leave us hanging: they deploy HSPs, our cellular “paramedics,” to come refold the misshapen protein and help get the cell running again. This process supports protein homeostasis, critical for the balanced, healthy functioning of our cells.
Unfortunately? One type of cell is particularly bad at inducing HSPs in times of stress, even in healthy people: motor neurons.
By the same token, drugs that boost the role of HSPs in repairing damaged cells in other parts of the body don’t seem to work as well in motor neurons – the site of misfolded proteins in people living with ALS.
With the help of her 2022 Discovery Grant, Dr. Vera Ugalde will look closely at why motor neurons are so bad at making HSPs, exploring an entirely new mechanism that could explain the problem.
“Dr. Vera Ugalde’s research could pave the way for groundbreaking discoveries in motor neuron research,” says Dr. Viviane Poupon, President and CEO of Brain Canada.
Her hope is that by finding out the exact reason HSPs work poorly in motor neurons – and why current drugs don’t seem to help – she can help open a new pathway for future therapeutics.
“We have to do this”
The project started when Dr. Vera Ugalde began speaking with her McGill colleague, long-time ALS researcher Dr. Heather Durham, who is also an expert on HSPs.
The two realized quickly that Dr. Vera Ugalde’s technical expertise on protein homeostasis complemented Dr. Durham’s deep understanding of the pathways leading to cellular damage in ALS.
“When we started talking, we said, ‘we have to do this,’” Dr. Vera Ugalde says. “It’s a good synergy.”
The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.
ALS Canada’s mission is to improve the lives of people affected by ALS through support, advocacy, and investment in research for a future without ALS.
Meet the researchers behind the winning 2022 Discovery Grant projects
What role does its sister protein play when restoring G3BP1 levels as a potential ALS treatment strategy?
Award: $125,000
Collaborators: Dr. Marlene Oeffinger, Institut de recherches cliniques de Montréal (IRCM)
Dr. Christine Vande Velde is a cellular biologist at the Centre de recherche du CHUM, Université de Montreal, and one of nine ALS Canada-Brain Canada Discovery Grant recipients for 2022. While she and her team spend their lab hours parsing out biological intricacies, her work is always motivated by something bigger: the lives of people affected by ALS.
Dr. Vande Velde just finished her six-year term on the ALS Society of Canada’s Board of Directors, which has given her face-to-face experiences with people living with ALS and their families.
“It’s been a fabulous experience that changed the way I think about what ALS Canada does. It has helped me always keep the mission front of mind,” she says.
For more than a decade, Dr. Vande Velde’s lab has been part of driving ALS research forward in Canada.
With this award, the research team will seek to understand the function of two “twin” proteins called G3BP1 and G3BP2. The proposal emerged from conversations between two trainees in her lab, a promising sign for the future of Canadian ALS research.
Conventional knowledge would say the two proteins are so similar, they’re identical. But other researchers have shown the prevailing narrative may be wrong, as previous studies reveal that when G3BP1 levels are reduced, G3BP2 cannot fully compensate for the loss.
G3BP1 tends to degrade when a protein called TDP-43 leaves its home in the nucleus – one of the most common hallmarks of ALS and other neurodegenerative diseases. Its twin, G3BP2, does not.
Dr. Vande Velde’s project asks a number of questions about what G3BP1 might do that its sibling can’t, if restoring G3BP1 function might be a therapeutic target for ALS, and more.
“In research, we can’t rely on overgeneralizations (like assuming two “twin” genes have the same function),” she says. “I’m excited to go deep into the biology to understand the nuances. In treatment, the details matter.”
“Regardless of the results, we will learn something about a target we think is druggable and relevant to the disease that we didn’t know before,” she says.
“Dr. Vande Velde is playing a pivotal role in shaping the future of ALS research in Canada. Her ability to think outside of the box makes her a valuable asset in the quest for innovative solutions and advancements,” says Dr. Viviane Poupon, President and CEO of Brain Canada.
“The more we understand the biology, the better we can interpret the results of any clinical trial,” says Dr. David Taylor, Vice-President, Research and Strategic Partnerships, ALS Canada. This is particularly important, as the research will help inform therapeutic strategies that Dr. Vande Velde is also working on in her lab.
At the end of the day, Dr. Vande Velde says she’s grateful to be part of such a robust research community – one that in recent years is producing real therapeutic results for patients.
“I don’t know anybody who works in ALS who’s not dedicated to the cause. Nobody does it as a hobby,” she says.
The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.
ALS Canada’s mission is to improve the lives of people affected by ALS through support, advocacy, and investment in research for a future without ALS.
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