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.
CAPTURE (Comprehensive Analysis Platform To Understand, Remedy, and Eliminate) ALS is a platform established in Canada to gather biological samples, data, and experiences of people with ALS and healthy volunteers from across the country.
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.
Updated October 20, 2017
Staying active and independent for as long as possible is important for people living with ALS as the disease progresses. There are many ways in which to manage symptoms or receive care, but there often isn’t enough research performed to determine which approaches make the greatest difference.
To help address these knowledge gaps and pave the way for better care, ALS Canada funds Clinical Management Grants thanks to donations from the Ice Bucket Challenge. So far, two clinical management grants have been awarded: one that focuses on helping people living with ALS to drive safely for longer, and another that is researching the use of cannabis (marijuana) to help manage pain and discomfort.
Driving Assessment: Helping People with ALS to Drive Safely, Longer
Associated with independence, driving is a complex activity that requires physical, emotional and mental focus. Unfortunately, many of these abilities decline as ALS progresses. Unlike other diseases like stroke or Parkinson’s, there are few published resources to measure when a person’s ALS has progressed to the point that driving becomes unsafe. As a result, ALS clinical care teams regularly face decisions about when to discuss driving with patients and families, whether someone living with ALS can drive safely, or if a referral for an on-road test is needed.
A retrospective review conducted by members of the ALS Clinic at the Montreal Neurological Institute & Hospital (MNI/H) found that many people with ALS were not making changes to their vehicles that had the potential to enable them to prolong driving: for example, adapted foot controls can help with pedal access, a ball installed on the steering wheel can help with steering; and a BiPAP machine secured in the vehicle can help with breathing.
To help empower people living with ALS, the clinic at the MNI/H, led by Dr. Angela Genge, is implementing a multidisciplinary, systematic approach to assess driving safety. “This initiative focuses on how the whole care team can help people with ALS drive safely for a longer length of time,” said Kendra Berry, the clinic’s occupational therapist, in an interview with ALS Canada.
Berry, who recognized the gap in care several years ago, is collaborating with the entire MNI/H multidisciplinary ALS clinic team on this initiative. After reviewing existing broad guidelines for other conditions, the clinical team is trying to establish a standardized driving assessment to be used in their clinical setting. The complete assessment incorporates the ALSFRS-R, a cognitive behavioural screen, and questionnaires for people with ALS and caregivers. Berry has also accumulated a battery of tasks to simulate driving actions that she is incorporating into regular clinic assessments.
With all this input, the team will develop checkpoints that the whole care team can use to help people with ALS decide when they may benefit from an adaptation, need to be referred for a road test or transition to giving up driving.
“We start the conversation at the first or second visit, rather than the usual timing of a year or two after diagnosis,” said Berry. Earlier discussion and driving assessment mean that people with ALS are empowered to access driving adaptations earlier.
The project is set to launch the week of August 28, 2017, and the team will follow about 200 study participants for two years. When the project is complete, they plan to share their learning with ALS clinicians across Canada and the SAAQ in Quebec, the provincial licensing authority for drivers’ licenses, which could help pave the way for other provincial and national groups to adopt them in the future.
Studying the use of cannabis extracts to manage ALS pain and discomfort
In surveys, people with ALS have reported that cannabis (marijuana) helps to alleviate weakness, speech difficulties, excessive saliva production, difficulty swallowing, breathing issues, pain and stiff muscles, and can improve sleep, appetite and mood.
Yet while cannabis has been used for symptom management by anywhere from 15 to 40 per cent of people with HIV/AIDS, epilepsy, chronic pain, multiple sclerosis and ALS, often the doctors providing care aren’t aware that their patients are using it.
In 2012, ALSUntangled conducted a review of cannabis studies and potential in ALS.
Studies of the effect of cannabis on ALS to date have used animal models or small numbers of people with single doses of only one ingredient – whereas cannabis contains over 480 compounds. The two most well-known active ingredients are tetrahydrocannabinol (THC), the psychoactive component that has been linked to analgetic action, appetite stimulation, decreased muscle stiffness and improved sleep; and cannabidiol (CBD), which has been studied for anti-inflammatory, anti-anxiety and anti-nausea benefits.
“THC, CBD and other ingredients in cannabis affect many different systems in the body,” said Dr. Mark Ware during the ALS Canada Virtual Research Forum on August 9, 2017. “For example, THC works by binding to a specific receptor found in the brain, spinal cord, the gastrointestinal tract and other body tissues. By affecting these receptors, cannabis has an impact on the ways our nerves talk to one another.”
Dr. Ware has been conducting cannabis research for medical purposes for almost 18 years, mostly in the area of pain management. He is executive director of the Canadian Consortium for the Investigation of Cannabinoids, director of Clinical Research at McGill University Health Centre’s Alan Edwards Pain Management Unit, and an associate professor in the Departments of Family Medicine and Anesthesia at McGill University in Montreal, Quebec.
With a clinical management grant through the ALS Canada Research Program, Dr. Ware is leading a team of Canadian researchers who will conduct a pilot study of the use of cannabis in 32 people with ALS starting later this fall. The other co-investigators include Dr. Angela Genge, director of the ALS Clinic and Clinical Research Unit at the MNI in Montreal, Quebec, and Dr. Colleen O’Connell, a neurologist specializing in physical medicine and rehabilitation who leads the ALS Clinic at the Stan Cassidy Centre for Rehabilitation in Fredericton, New Brunswick and is an assistant professor at Dalhousie University in Halifax, Nova Scotia.
The researchers are working with Green Sky Labs, a Canadian company licensed by Health Canada to grow marijuana for medicinal purposes, to obtain oral capsule products with different ratios of THC and CBD formulated in a medical-grade oil. Study participants with ALS will be part of a crossover study over an eight week period, with five days on one dose, followed by a nine day washout period, then another five days on a different dose, until all four ratios have been administered. Researchers will collect information about ALS symptoms, pain, mood, sleep, appetite, cardiovascular and respiratory effects, and any adverse effects.
Health Canada is currently reviewing Green Sky Labs’ application for product approval. The researchers expect to begin the study by the early 2018. Results from this pilot study will inform future research studies that could seek to explore whether cannabis can slow disease progression.
Clinical Management Grants are one category of high-quality research funded through the ALS Canada Research Program. Read more about the ALS Canada Research Program and consider donating today.
ALS Canada Virtual Research Forum
Update: Dr. Ware was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.
ALS is difficult to diagnose because no single test or procedure can firmly identify the disease. Current diagnostic tests for ALS focus on ruling out other diseases that share similar initial symptoms. For example, magnetic resonance imaging (MRI) is a test typically used to eliminate a diagnosis of cancer, multiple sclerosis or pressure on the spinal cord due to arthritis. A standard MRI analysis of a person with ALS, however, usually shows normal results.
The lack of a reliable diagnostic test for ALS means that it takes on average about a year for a diagnosis to be confirmed. “The delay means we can’t help people sooner, nor identify them early enough to enter a clinical trial,” said Dr. Sanjay Kalra in an interview with ALS Canada. “This issue is actually hindering the clinical investigation of drug therapies. If we could identify people with different types and progressions of ALS more quickly, we could find a breakthrough therapy faster. A test is desperately needed that can determine if a drug is working in clinical trial.” Dr. Kalra is a professor in the department of medicine (neurology) and member of the Neuroscience and Mental Health Institute at the University of Alberta.
Looking for ALS in Brain Images
Dr. Kalra has been intrigued with finding a way to harness the power of imaging to uncover the early signs of ALS since his medical residency when he met neurologist Dr. Douglas Arnold, an MRI specialist at the Montréal Neurological Institute and Hospital. “My residency research rotation was only supposed to last six months, but after realizing the potential power of this technology in research and really enjoying working with people with ALS, I decided to continue and eventually stayed as a postdoctoral fellow specializing in MRI for ALS,” said Dr. Kalra.
Dr. Kalra has secured funding for his imaging research program from a number of sponsors including the Canadian Institutes of Health Research (CIHR), the major agency of the Canadian government responsible for funding health research in Canada. His focus has been to develop and validate advanced MRI methods that can be used as a biomarker, a biological marker that allows physicians to detect disease earlier, monitor disease progression and evaluate new therapies.
In 2013 he founded the Canadian ALS Neuroimaging Consortium (CALSNIC), a multidisciplinary team of experts from across Canada that includes neurologists, MRI scientists, computing scientists, neuropathologists and a biostatistician. Since then, the CALSNIC team has been working together on a national scale to develop advanced MRI methods to find biomarkers in people with ALS and related conditions.
Dr. Kalra and three colleagues at the University of Alberta in Edmonton conducted a preliminary study in 2014-2015 to look for biomarkers in brain images using MRI scans of 19 people with ALS and 20 healthy participants for comparison. They analyzed the images with 3D texture analysis, an advanced method that allowed them to look for statistically significant patterns of brain degeneration not normally visible to the naked eye. They examined voxels, tiny 3D spaces in the brain about a cubic millimetre in size.
The researchers found different texture features in regions of the brain affected by ALS and frontotemporal dementia in people with ALS compared to people without ALS. They also discovered that some features were associated with clinical observations, such as disease duration and differences in finger tapping speed. The study was funded in part by an ALS Canada Discovery Grant.
Going Big: The First Large Imaging Study in the World
Based on encouraging research results in this preliminary study and other work, Dr. Kalra wants to confirm the findings in a larger group of people with ALS. “The ALS field has seen an explosion of imaging studies in the last five years, but for the most part, they have been single-centre studies that used different methods in small groups of patients, so it has been difficult to draw conclusions on the best method to use,” he said. “To develop and validate the use of MRI biomarkers , especially for their potential use in clinical trials, we need to confirm that our these methods will work well on a large scale, in every clinic.”
In 2015, Dr. Kalra and a team of 13 other investigators applied for a grant from ALS Canada and were successful. The resulting ALS Canada – Brain Canada Arthur J. Hudson Translational Team Grant of $2.94 million – the largest grant awarded in ALS Canada’s history – is funding the first large multicentre imaging study focused on ALS in the world, according to Dr. Kalra. The study seeks to enroll over 700 volunteers split between people with ALS and people without ALS for comparison in seven locations: Calgary, Edmonton, Vancouver, London, Toronto, Montreal and Quebec City. Some sites are currently recruiting and others will be up and running soon. Participants receive a baseline MRI and clinical evaluation followed by two follow-up visits.
Always thinking ahead, Dr. Kalra is already considering how to expand CALSNIC further to increase the value of the network. “Another purpose of setting up the CALSNIC infrastructure is that it allows us to probe other questions. I’m excited that it has spurred other ALS research and collaborations,” said Dr. Kalra, “such as at the University of Toronto where Dr. Yana Yunusova is studying speech changes in patients across the CALSNIC network and will be able to compare the findings with our imaging data. In the future, I would like to see CALSNIC build a comprehensive resource of tissue, imaging and clinical descriptions that all scientists can access to understand the disease better.”
ALS Canada has been funding world-class research across Canada for over 30 years to enable discovery of new treatments and therapeutic interventions that have the potential to make an impact on altering the course of the disease or improving the quality of life for people with ALS.
Read more about the ALS Canada Research Program and consider donating today.